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Can Newborn Screening for Krabbe Disease Lead to New Therapies?
KANSAS CITY, MO—Newborn screening for Krabbe disease, also known as globoid-cell leukodystrophy (GLD), may help researchers evaluate potential therapies for this condition, according to an overview presented at the 46th Annual Meeting of the Child Neurology Society. Early diagnosis likely is needed to effectively intervene, especially in rapidly progressive forms of the disease, said Gustavo H. B. Maegawa, MD, PhD, Associate Professor of Neuroscience in the Department of Pediatrics at the University of Florida’s College of Medicine in Gainesville.
A Severe Condition
Krabbe disease is a lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. The incidence is approximately one in 100,000 births. The carrier frequency is approximately one in 150. Krabbe disease is panethnic, and high incidence has been observed in inbred populations.
In the United States, 85% to 90% of patients with Krabbe disease have the infantile form, with onset of symptoms occuring before age 6 months. Stage I symptoms of infantile Krabbe disease include irritability, stiffness, developmental delay, feeding problems, and seizures. Stage II symptoms include rapid neurodegeneration with hypertonicity of the upper and lower extremities, optic atrophy, wheel-chair bound, hyporeflexia, and worsening of dysphagia requiring tube feeding. During stage III, affected patients become immobile, go blind, and eventually enter a vegetative state. Most cases are infantile and progress “so fast that the child dies before 10 or 12 months of age,” said Dr. Maegawa.
Late-onset forms of Krabbe disease include late-infantile Krabbe disease, with onset between age 6 months and 2 years; juvenile onset, which occurs between ages 3 and 8; and adult-onset, which occurs after age 8. “No consistent correlation has been observed between age of onset and residual GALC enzyme activity measured in peripheral leukocytes,” said Dr. Maegawa.
However, some correlations are observed when GALC enzymatic activity is measured from culture primary fibroblasts (derived from skin biopsies) from patients with different clincial forms of GLD. In GALC from these cells, a higher residual GALC activity is detected in cultured fibroblasts from patients with late-onset forms of GLD.
EEGs for patients with Krabbe disease initially appear normal, although they can have background activity that is slow and disorganized. Given that in GLD, the myelin-forming cells are severely affected in both central and peripheral nervous systems (oligodendrocytes and Schwann cells, respectively), nerve conduction velocities are consistently low, especially in patients with peripheral neuropathy, said Dr. Maegawa. In addition, visual and auditory evoked responses are severely abnormal in patients with early-infantile onset.
Current Treatment and Newborn Screening
In 2005, Escolar et al reported that hematopoietic stem cell transplantation (HSCT) favorably altered the natural history of the disease in asymptomatic newborns with infantile Krabbe disease, whereas HSCT after symptoms had developed did not result in substantive neurologic improvement. This finding set the stage for newborn screening programs for Krabbe disease.
New York State began screening all newborns for Krabbe disease in 2006. Wasserstein et al examined the clinical outcomes of infants screened for Krabbe disease in the state. Of the nearly two million infants screened, five were diagnosed with early-infantile Krabbe disease, and three died. Two babies died from HSCT-related complications, and one died from untreated disease. In addition, screening identified 92 infants with low risk of the disease, 37 with moderate risk, and 14 with high risk.
Initially, infants with confirmatory residual GALC activities between 0.30 and 0.5 nmol/hour/mg protein were considered to be at low-risk. Later on, with the experience of repeating the GALC activity, infants with activities greater than 0.3 nmol/hour/mg are now considered to not be at risk unless they carry two potentially pathogenic variants, which would classify them as moderate risk. In the moderate-risk category, newborns present confirmatory GALC activity of 0.16 to 0.29 nmol/hour/mg protein or GALC activity in the low-risk range but two known or potentially pathogenic mutations in the GALC gene.
In the high-risk category, newborns show high risk for Krabbe disease based on very low confirmatory GALC activity of 0.0 to 0.15-nmol/hour/mg protein. All infants in this group underwent urgent neurodiagnostic evaluation that included a neurologic exam every month, neuroimaging at 0, four, eight, and 12 months until 12 months. Between 13 and 36 months of age, the neurologic exams are every three months and brain imaging as needed.
The incidence of infantile Krabbe disease in New York, one in 394,000, was lower than anticipated. Researchers also observed significant overlap between risk categories. A few children switched from high to moderate risk groups. Finally, there was low compliance with the Krabbe Consortium protocol.
Seeking Therapies
Researchers are using cell-based high-throughput screening (HTS) assays to discover potential treatments for Krabbe disease. One proposed HTS assay is performed in cell-lines with the human GALC mutated protein with a specific flurogenic substrate also used to measure the GALC activity in dried blood spots in newborn screens for Krabbe disease, said Dr. Maegawa.
Another developed throughput assay is cell-based but uses neurologically relevant brain cells and measures accumulated psychosine, a cytotoxic natural substrate in Krabbe disease. The cell-line was established from the brain of naturally occuring mouse models for Krabbe disease called the Twitcher mouse.
This is an essential component of the myelin, but at nonphysiological high levels, psychosine becomes extremely toxic to myelin-forming cells, such as oligodendrocytes and Schwann cells.
“We are also looking at the manipulation of the biosynthetic psychosine, which is the extremely cytotoxic metabolite in Krabbe disease. If we find a molecule that normalizes the levels of psychosine, we will eventually be able to find a drug that will prevent the cytotoxicity of high levels found in Krabbe disease and to eventually arrest and prevent the demyelination that occurs in this disease,” said Dr. Maegawa.
“Gene therapy and cell therapy trials have shown progress in the Twitcher models by carrying a homozygous nonsense mutation in the GALC murine gene. Hopefully, a combination of these approaches will soon be used in clinical trials.”
—Erica Tricarico
Suggested Reading
Escolar ML, Poe MD, Provenzale JM, et al. Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Eng J Med. 2005;352(20):2069-2081.
Jang DS, Ye W, Guimei T, et al. Cell-based high-throughput screening identifies galactocerebrosidase enhancers as potential small-molecule therapies for Krabbe disease. J Neurosci Res. 2016;94(11):1231-1245.
Ribbens J, Whiteley G, Furuya F, et al. A high-throughput screening assay using Krabbe disease patient cells. Anal Biochem. 2013;434(1):15-25.
Ribbens JJ, Moser AB, Hubbard WC, et al. Characterization and application of a disease-cell model for neurodegenerative lysosomal disease. Mol Genet Metab. 2014;111(2):172-183.
Wasserstein M, Andriola M, Arnold G, et al. Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State. Genet Med. 2016;18(12):1235-1243.
KANSAS CITY, MO—Newborn screening for Krabbe disease, also known as globoid-cell leukodystrophy (GLD), may help researchers evaluate potential therapies for this condition, according to an overview presented at the 46th Annual Meeting of the Child Neurology Society. Early diagnosis likely is needed to effectively intervene, especially in rapidly progressive forms of the disease, said Gustavo H. B. Maegawa, MD, PhD, Associate Professor of Neuroscience in the Department of Pediatrics at the University of Florida’s College of Medicine in Gainesville.
A Severe Condition
Krabbe disease is a lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. The incidence is approximately one in 100,000 births. The carrier frequency is approximately one in 150. Krabbe disease is panethnic, and high incidence has been observed in inbred populations.
In the United States, 85% to 90% of patients with Krabbe disease have the infantile form, with onset of symptoms occuring before age 6 months. Stage I symptoms of infantile Krabbe disease include irritability, stiffness, developmental delay, feeding problems, and seizures. Stage II symptoms include rapid neurodegeneration with hypertonicity of the upper and lower extremities, optic atrophy, wheel-chair bound, hyporeflexia, and worsening of dysphagia requiring tube feeding. During stage III, affected patients become immobile, go blind, and eventually enter a vegetative state. Most cases are infantile and progress “so fast that the child dies before 10 or 12 months of age,” said Dr. Maegawa.
Late-onset forms of Krabbe disease include late-infantile Krabbe disease, with onset between age 6 months and 2 years; juvenile onset, which occurs between ages 3 and 8; and adult-onset, which occurs after age 8. “No consistent correlation has been observed between age of onset and residual GALC enzyme activity measured in peripheral leukocytes,” said Dr. Maegawa.
However, some correlations are observed when GALC enzymatic activity is measured from culture primary fibroblasts (derived from skin biopsies) from patients with different clincial forms of GLD. In GALC from these cells, a higher residual GALC activity is detected in cultured fibroblasts from patients with late-onset forms of GLD.
EEGs for patients with Krabbe disease initially appear normal, although they can have background activity that is slow and disorganized. Given that in GLD, the myelin-forming cells are severely affected in both central and peripheral nervous systems (oligodendrocytes and Schwann cells, respectively), nerve conduction velocities are consistently low, especially in patients with peripheral neuropathy, said Dr. Maegawa. In addition, visual and auditory evoked responses are severely abnormal in patients with early-infantile onset.
Current Treatment and Newborn Screening
In 2005, Escolar et al reported that hematopoietic stem cell transplantation (HSCT) favorably altered the natural history of the disease in asymptomatic newborns with infantile Krabbe disease, whereas HSCT after symptoms had developed did not result in substantive neurologic improvement. This finding set the stage for newborn screening programs for Krabbe disease.
New York State began screening all newborns for Krabbe disease in 2006. Wasserstein et al examined the clinical outcomes of infants screened for Krabbe disease in the state. Of the nearly two million infants screened, five were diagnosed with early-infantile Krabbe disease, and three died. Two babies died from HSCT-related complications, and one died from untreated disease. In addition, screening identified 92 infants with low risk of the disease, 37 with moderate risk, and 14 with high risk.
Initially, infants with confirmatory residual GALC activities between 0.30 and 0.5 nmol/hour/mg protein were considered to be at low-risk. Later on, with the experience of repeating the GALC activity, infants with activities greater than 0.3 nmol/hour/mg are now considered to not be at risk unless they carry two potentially pathogenic variants, which would classify them as moderate risk. In the moderate-risk category, newborns present confirmatory GALC activity of 0.16 to 0.29 nmol/hour/mg protein or GALC activity in the low-risk range but two known or potentially pathogenic mutations in the GALC gene.
In the high-risk category, newborns show high risk for Krabbe disease based on very low confirmatory GALC activity of 0.0 to 0.15-nmol/hour/mg protein. All infants in this group underwent urgent neurodiagnostic evaluation that included a neurologic exam every month, neuroimaging at 0, four, eight, and 12 months until 12 months. Between 13 and 36 months of age, the neurologic exams are every three months and brain imaging as needed.
The incidence of infantile Krabbe disease in New York, one in 394,000, was lower than anticipated. Researchers also observed significant overlap between risk categories. A few children switched from high to moderate risk groups. Finally, there was low compliance with the Krabbe Consortium protocol.
Seeking Therapies
Researchers are using cell-based high-throughput screening (HTS) assays to discover potential treatments for Krabbe disease. One proposed HTS assay is performed in cell-lines with the human GALC mutated protein with a specific flurogenic substrate also used to measure the GALC activity in dried blood spots in newborn screens for Krabbe disease, said Dr. Maegawa.
Another developed throughput assay is cell-based but uses neurologically relevant brain cells and measures accumulated psychosine, a cytotoxic natural substrate in Krabbe disease. The cell-line was established from the brain of naturally occuring mouse models for Krabbe disease called the Twitcher mouse.
This is an essential component of the myelin, but at nonphysiological high levels, psychosine becomes extremely toxic to myelin-forming cells, such as oligodendrocytes and Schwann cells.
“We are also looking at the manipulation of the biosynthetic psychosine, which is the extremely cytotoxic metabolite in Krabbe disease. If we find a molecule that normalizes the levels of psychosine, we will eventually be able to find a drug that will prevent the cytotoxicity of high levels found in Krabbe disease and to eventually arrest and prevent the demyelination that occurs in this disease,” said Dr. Maegawa.
“Gene therapy and cell therapy trials have shown progress in the Twitcher models by carrying a homozygous nonsense mutation in the GALC murine gene. Hopefully, a combination of these approaches will soon be used in clinical trials.”
—Erica Tricarico
Suggested Reading
Escolar ML, Poe MD, Provenzale JM, et al. Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Eng J Med. 2005;352(20):2069-2081.
Jang DS, Ye W, Guimei T, et al. Cell-based high-throughput screening identifies galactocerebrosidase enhancers as potential small-molecule therapies for Krabbe disease. J Neurosci Res. 2016;94(11):1231-1245.
Ribbens J, Whiteley G, Furuya F, et al. A high-throughput screening assay using Krabbe disease patient cells. Anal Biochem. 2013;434(1):15-25.
Ribbens JJ, Moser AB, Hubbard WC, et al. Characterization and application of a disease-cell model for neurodegenerative lysosomal disease. Mol Genet Metab. 2014;111(2):172-183.
Wasserstein M, Andriola M, Arnold G, et al. Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State. Genet Med. 2016;18(12):1235-1243.
KANSAS CITY, MO—Newborn screening for Krabbe disease, also known as globoid-cell leukodystrophy (GLD), may help researchers evaluate potential therapies for this condition, according to an overview presented at the 46th Annual Meeting of the Child Neurology Society. Early diagnosis likely is needed to effectively intervene, especially in rapidly progressive forms of the disease, said Gustavo H. B. Maegawa, MD, PhD, Associate Professor of Neuroscience in the Department of Pediatrics at the University of Florida’s College of Medicine in Gainesville.
A Severe Condition
Krabbe disease is a lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. The incidence is approximately one in 100,000 births. The carrier frequency is approximately one in 150. Krabbe disease is panethnic, and high incidence has been observed in inbred populations.
In the United States, 85% to 90% of patients with Krabbe disease have the infantile form, with onset of symptoms occuring before age 6 months. Stage I symptoms of infantile Krabbe disease include irritability, stiffness, developmental delay, feeding problems, and seizures. Stage II symptoms include rapid neurodegeneration with hypertonicity of the upper and lower extremities, optic atrophy, wheel-chair bound, hyporeflexia, and worsening of dysphagia requiring tube feeding. During stage III, affected patients become immobile, go blind, and eventually enter a vegetative state. Most cases are infantile and progress “so fast that the child dies before 10 or 12 months of age,” said Dr. Maegawa.
Late-onset forms of Krabbe disease include late-infantile Krabbe disease, with onset between age 6 months and 2 years; juvenile onset, which occurs between ages 3 and 8; and adult-onset, which occurs after age 8. “No consistent correlation has been observed between age of onset and residual GALC enzyme activity measured in peripheral leukocytes,” said Dr. Maegawa.
However, some correlations are observed when GALC enzymatic activity is measured from culture primary fibroblasts (derived from skin biopsies) from patients with different clincial forms of GLD. In GALC from these cells, a higher residual GALC activity is detected in cultured fibroblasts from patients with late-onset forms of GLD.
EEGs for patients with Krabbe disease initially appear normal, although they can have background activity that is slow and disorganized. Given that in GLD, the myelin-forming cells are severely affected in both central and peripheral nervous systems (oligodendrocytes and Schwann cells, respectively), nerve conduction velocities are consistently low, especially in patients with peripheral neuropathy, said Dr. Maegawa. In addition, visual and auditory evoked responses are severely abnormal in patients with early-infantile onset.
Current Treatment and Newborn Screening
In 2005, Escolar et al reported that hematopoietic stem cell transplantation (HSCT) favorably altered the natural history of the disease in asymptomatic newborns with infantile Krabbe disease, whereas HSCT after symptoms had developed did not result in substantive neurologic improvement. This finding set the stage for newborn screening programs for Krabbe disease.
New York State began screening all newborns for Krabbe disease in 2006. Wasserstein et al examined the clinical outcomes of infants screened for Krabbe disease in the state. Of the nearly two million infants screened, five were diagnosed with early-infantile Krabbe disease, and three died. Two babies died from HSCT-related complications, and one died from untreated disease. In addition, screening identified 92 infants with low risk of the disease, 37 with moderate risk, and 14 with high risk.
Initially, infants with confirmatory residual GALC activities between 0.30 and 0.5 nmol/hour/mg protein were considered to be at low-risk. Later on, with the experience of repeating the GALC activity, infants with activities greater than 0.3 nmol/hour/mg are now considered to not be at risk unless they carry two potentially pathogenic variants, which would classify them as moderate risk. In the moderate-risk category, newborns present confirmatory GALC activity of 0.16 to 0.29 nmol/hour/mg protein or GALC activity in the low-risk range but two known or potentially pathogenic mutations in the GALC gene.
In the high-risk category, newborns show high risk for Krabbe disease based on very low confirmatory GALC activity of 0.0 to 0.15-nmol/hour/mg protein. All infants in this group underwent urgent neurodiagnostic evaluation that included a neurologic exam every month, neuroimaging at 0, four, eight, and 12 months until 12 months. Between 13 and 36 months of age, the neurologic exams are every three months and brain imaging as needed.
The incidence of infantile Krabbe disease in New York, one in 394,000, was lower than anticipated. Researchers also observed significant overlap between risk categories. A few children switched from high to moderate risk groups. Finally, there was low compliance with the Krabbe Consortium protocol.
Seeking Therapies
Researchers are using cell-based high-throughput screening (HTS) assays to discover potential treatments for Krabbe disease. One proposed HTS assay is performed in cell-lines with the human GALC mutated protein with a specific flurogenic substrate also used to measure the GALC activity in dried blood spots in newborn screens for Krabbe disease, said Dr. Maegawa.
Another developed throughput assay is cell-based but uses neurologically relevant brain cells and measures accumulated psychosine, a cytotoxic natural substrate in Krabbe disease. The cell-line was established from the brain of naturally occuring mouse models for Krabbe disease called the Twitcher mouse.
This is an essential component of the myelin, but at nonphysiological high levels, psychosine becomes extremely toxic to myelin-forming cells, such as oligodendrocytes and Schwann cells.
“We are also looking at the manipulation of the biosynthetic psychosine, which is the extremely cytotoxic metabolite in Krabbe disease. If we find a molecule that normalizes the levels of psychosine, we will eventually be able to find a drug that will prevent the cytotoxicity of high levels found in Krabbe disease and to eventually arrest and prevent the demyelination that occurs in this disease,” said Dr. Maegawa.
“Gene therapy and cell therapy trials have shown progress in the Twitcher models by carrying a homozygous nonsense mutation in the GALC murine gene. Hopefully, a combination of these approaches will soon be used in clinical trials.”
—Erica Tricarico
Suggested Reading
Escolar ML, Poe MD, Provenzale JM, et al. Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Eng J Med. 2005;352(20):2069-2081.
Jang DS, Ye W, Guimei T, et al. Cell-based high-throughput screening identifies galactocerebrosidase enhancers as potential small-molecule therapies for Krabbe disease. J Neurosci Res. 2016;94(11):1231-1245.
Ribbens J, Whiteley G, Furuya F, et al. A high-throughput screening assay using Krabbe disease patient cells. Anal Biochem. 2013;434(1):15-25.
Ribbens JJ, Moser AB, Hubbard WC, et al. Characterization and application of a disease-cell model for neurodegenerative lysosomal disease. Mol Genet Metab. 2014;111(2):172-183.
Wasserstein M, Andriola M, Arnold G, et al. Clinical outcomes of children with abnormal newborn screening results for Krabbe disease in New York State. Genet Med. 2016;18(12):1235-1243.
FDA approves implantable therapy for PAH
to treat adult patients with New York Heart Association (NYHA) Class I, II and III pulmonary arterial hypertension.
This infusion system is implanted into a patient for intravenous delivery of treprostinil (Remodulin) and is designed to help supply blood to the lungs and keep a patient’s blood pressure within a healthy range. The system comprises three parts: the pump, the programmer, and the catheter.
The implant should not be used for patients with NYHA Class IV heart failure, a known or suspected infection, bacteremia, or sepsis requiring antibiotics; vasculature that is inadequate for an 8 French introducer or catheter advancement without stylet guidance; implanted leads or catheters (active or abandoned) in the superior vena cava that cannot be removed prior to or at system implant; a body size not sufficient to accept the pump; or skin or soft tissue that would heal poorly or increase susceptibility to infections. Patients who are unable to tolerate a sudden cessation of treprostinil therapy also would not be able to receive the implantable device.
Read the full approval on the FDA’s website.
to treat adult patients with New York Heart Association (NYHA) Class I, II and III pulmonary arterial hypertension.
This infusion system is implanted into a patient for intravenous delivery of treprostinil (Remodulin) and is designed to help supply blood to the lungs and keep a patient’s blood pressure within a healthy range. The system comprises three parts: the pump, the programmer, and the catheter.
The implant should not be used for patients with NYHA Class IV heart failure, a known or suspected infection, bacteremia, or sepsis requiring antibiotics; vasculature that is inadequate for an 8 French introducer or catheter advancement without stylet guidance; implanted leads or catheters (active or abandoned) in the superior vena cava that cannot be removed prior to or at system implant; a body size not sufficient to accept the pump; or skin or soft tissue that would heal poorly or increase susceptibility to infections. Patients who are unable to tolerate a sudden cessation of treprostinil therapy also would not be able to receive the implantable device.
Read the full approval on the FDA’s website.
to treat adult patients with New York Heart Association (NYHA) Class I, II and III pulmonary arterial hypertension.
This infusion system is implanted into a patient for intravenous delivery of treprostinil (Remodulin) and is designed to help supply blood to the lungs and keep a patient’s blood pressure within a healthy range. The system comprises three parts: the pump, the programmer, and the catheter.
The implant should not be used for patients with NYHA Class IV heart failure, a known or suspected infection, bacteremia, or sepsis requiring antibiotics; vasculature that is inadequate for an 8 French introducer or catheter advancement without stylet guidance; implanted leads or catheters (active or abandoned) in the superior vena cava that cannot be removed prior to or at system implant; a body size not sufficient to accept the pump; or skin or soft tissue that would heal poorly or increase susceptibility to infections. Patients who are unable to tolerate a sudden cessation of treprostinil therapy also would not be able to receive the implantable device.
Read the full approval on the FDA’s website.
Patient instructions in surgery exceed recommended reading grade level
JACKSONVILLE, FLA. – The American Medical Association and National Institutes of Health recommend that patient instructions should be written at a sixth-grade level, and the Centers for Disease Control and Prevention recommend an eighth-grade level so patients and caregivers can easily understand them, but a study of education materials that patients get for surgery finds that they typically overshoot that mark – in some cases considerably.
A study of patient education materials distributed at the University of Alabama at Birmingham has revealed that the , second-year medical student Callie Perkins reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.
“Only 16% of our collected material actually met the standards for readability,” Ms. Perkins said. “As far as surgical subspecialties go, neurosurgery had the highest grade level and plastic surgery had the lowest.”
Nine of the 12 surgical disciplines had no materials at the sixth-grade level or below. Plastic surgery had the highest percentage of materials that met the recommended standard: 47%. Overall, plastic surgery education materials had the lowest FKGL score, at the equivalent of grade 6.34. Neurosurgery had the highest, at 9.83. Other disciplines with an FKGL of 9 or greater are thoracic surgery (9.61) and pancreatic surgery (9.18), while vascular surgery had a level of 8.95.
The study also looked at specific words commonly used in patient literature with FKGL scores that far exceed the recommended level, Ms. Perkins said. They include strenuous (21 FKGL), anesthesia (26.2 FKGL), narcotic (21.5 FKGL) and incision (16.8 FKGL).
The findings, Ms. Perkins said, “provide a clear opportunity for improvement of our patient materials at UAB.” She noted that Microsoft Word has a tool for evaluating the FKGL of text, although the software does not account for potentially more challenging anatomical terms.
Ms. Perkins suggested a way forward may be to hold focus groups with surgeons and nursing clinical care coordinators to educate them about more patient-friendly terminology. In the meantime, Ms. Perkins said, using the FKGL tool in Microsoft Word is the most accessible solution to gauge education materials that talk over the patient’s head.
Ms. Perkins reported having no financial relationships to disclose.
SOURCE: Perkins, C et al. Abstract 67.08
JACKSONVILLE, FLA. – The American Medical Association and National Institutes of Health recommend that patient instructions should be written at a sixth-grade level, and the Centers for Disease Control and Prevention recommend an eighth-grade level so patients and caregivers can easily understand them, but a study of education materials that patients get for surgery finds that they typically overshoot that mark – in some cases considerably.
A study of patient education materials distributed at the University of Alabama at Birmingham has revealed that the , second-year medical student Callie Perkins reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.
“Only 16% of our collected material actually met the standards for readability,” Ms. Perkins said. “As far as surgical subspecialties go, neurosurgery had the highest grade level and plastic surgery had the lowest.”
Nine of the 12 surgical disciplines had no materials at the sixth-grade level or below. Plastic surgery had the highest percentage of materials that met the recommended standard: 47%. Overall, plastic surgery education materials had the lowest FKGL score, at the equivalent of grade 6.34. Neurosurgery had the highest, at 9.83. Other disciplines with an FKGL of 9 or greater are thoracic surgery (9.61) and pancreatic surgery (9.18), while vascular surgery had a level of 8.95.
The study also looked at specific words commonly used in patient literature with FKGL scores that far exceed the recommended level, Ms. Perkins said. They include strenuous (21 FKGL), anesthesia (26.2 FKGL), narcotic (21.5 FKGL) and incision (16.8 FKGL).
The findings, Ms. Perkins said, “provide a clear opportunity for improvement of our patient materials at UAB.” She noted that Microsoft Word has a tool for evaluating the FKGL of text, although the software does not account for potentially more challenging anatomical terms.
Ms. Perkins suggested a way forward may be to hold focus groups with surgeons and nursing clinical care coordinators to educate them about more patient-friendly terminology. In the meantime, Ms. Perkins said, using the FKGL tool in Microsoft Word is the most accessible solution to gauge education materials that talk over the patient’s head.
Ms. Perkins reported having no financial relationships to disclose.
SOURCE: Perkins, C et al. Abstract 67.08
JACKSONVILLE, FLA. – The American Medical Association and National Institutes of Health recommend that patient instructions should be written at a sixth-grade level, and the Centers for Disease Control and Prevention recommend an eighth-grade level so patients and caregivers can easily understand them, but a study of education materials that patients get for surgery finds that they typically overshoot that mark – in some cases considerably.
A study of patient education materials distributed at the University of Alabama at Birmingham has revealed that the , second-year medical student Callie Perkins reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.
“Only 16% of our collected material actually met the standards for readability,” Ms. Perkins said. “As far as surgical subspecialties go, neurosurgery had the highest grade level and plastic surgery had the lowest.”
Nine of the 12 surgical disciplines had no materials at the sixth-grade level or below. Plastic surgery had the highest percentage of materials that met the recommended standard: 47%. Overall, plastic surgery education materials had the lowest FKGL score, at the equivalent of grade 6.34. Neurosurgery had the highest, at 9.83. Other disciplines with an FKGL of 9 or greater are thoracic surgery (9.61) and pancreatic surgery (9.18), while vascular surgery had a level of 8.95.
The study also looked at specific words commonly used in patient literature with FKGL scores that far exceed the recommended level, Ms. Perkins said. They include strenuous (21 FKGL), anesthesia (26.2 FKGL), narcotic (21.5 FKGL) and incision (16.8 FKGL).
The findings, Ms. Perkins said, “provide a clear opportunity for improvement of our patient materials at UAB.” She noted that Microsoft Word has a tool for evaluating the FKGL of text, although the software does not account for potentially more challenging anatomical terms.
Ms. Perkins suggested a way forward may be to hold focus groups with surgeons and nursing clinical care coordinators to educate them about more patient-friendly terminology. In the meantime, Ms. Perkins said, using the FKGL tool in Microsoft Word is the most accessible solution to gauge education materials that talk over the patient’s head.
Ms. Perkins reported having no financial relationships to disclose.
SOURCE: Perkins, C et al. Abstract 67.08
AT THE ACADEMIC SURGICAL CONGRESS
Key clinical point: Patient education materials in surgery typically exceed the recommended guidelines of being at a sixth-grade reading level.
Major finding: Only 16% of patient education materials from surgical specialties met the recommended guideline.
Data source: Flesch-Kincaid Grade Level analysis of 112 education materials collected from 12 different surgical specialties at the University of Alabama at Birmingham.
Disclosure: Ms. Perkins reported having no financial relationships to disclose.
Source: Perkins, C et al. Abstract 67.08.
Antihistamines still are prescribed inappropriately for atopic dermatitis
said Alice He, MD, at the Center for Dermatology Research, Wake Forest University, Winston-Salem, N.C., and her associates.
Results of double-blind, randomized trials have found that oral antihistamines do not effectively treat itch associated with atopic dermatitis (AD), and American Academy of Dermatology guidelines state that intermittent short-term use of sedating antihistamines may help insomnia secondary to itch, but should not be substituted for topical treatments in atopic dermatitis management (J Am Acad Dermatol. 2014;71[2]:327-49), the investigators said. Nonetheless, physicians continue to prescribe antihistamines to AD patients.
Sedating antihistamines accounted for the majority of antihistamines prescribed by pediatricians (58%) and dermatologists (70%) for AD. Nonsedating antihistamines accounted for the majority of the antihistamines prescribed by family physicians (84%), internists (100%), and other specialists (55%), the investigators said.
(The sedating antihistamines prescribed included hydroxyzine, diphenhydramine, chlorpheniramine, brompheniramine, and cyproheptadine; nonsedating antihistamines include cetirizine, desloratadine, levocetirizine, loratadine, and fexofenadine.)
Although the AAD guidelines allow intermittent, short-term use of sedating antihistamines to treat AD-associated itch, these medications may be harmful to sleep in terms of reduced sleep quality and decreased REM sleep. Also, studies have shown that their effects can persist into the daytime and have the potential to impair cognitive function, including learning and memory.
“Physicians should consider the potential risks when prescribing sedating antihistamines as adjunctive treatment for atopic dermatitis,” Dr. He and her associates warned in the article in the Journal of the American Academy of Dermatology.
The researchers took a look at the top ten comorbidities reported among visits for AD, because nonsedating antihistamines might have been prescribed for a different diagnosis. There were three conditions for which antihistamines may be indicated: allergic rhinitis (13%), dermatitis attributable to food (8.5%), and conjunctivitis (3%). This “validates antihistamine prescriptions for a maximum of only 24.5% of patients who received antihistamines, indicating that a large proportion of antihistamine prescriptions were prescribed specifically for AD,” they said.
The authors said that, “while histamine does not play a role in AD via H1R [histamine-1 receptor], it may still be relevant in AD pathogenesis through actions on its most recently described receptor, histamine-4 receptor (H4R).”
“The advent of new targeted systemic therapies, such as T-helper 2 cytokine antagonists and H4R antagonists,” may one day help fill “the unmet need for effective treatments for atopic dermatitis,” Dr. He and her associates concluded.
The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories. Dr. He listed no other relevant financial disclosures. Her coauthors disclosed research, speaking, and/or consulting support from a variety of pharmaceutical companies; one author is an employee of Abbvie.
SOURCE: He A et al. J Amer Acad of Dermatol. 2008. doi: 10.1016/j.jaad.2017.12.077.
said Alice He, MD, at the Center for Dermatology Research, Wake Forest University, Winston-Salem, N.C., and her associates.
Results of double-blind, randomized trials have found that oral antihistamines do not effectively treat itch associated with atopic dermatitis (AD), and American Academy of Dermatology guidelines state that intermittent short-term use of sedating antihistamines may help insomnia secondary to itch, but should not be substituted for topical treatments in atopic dermatitis management (J Am Acad Dermatol. 2014;71[2]:327-49), the investigators said. Nonetheless, physicians continue to prescribe antihistamines to AD patients.
Sedating antihistamines accounted for the majority of antihistamines prescribed by pediatricians (58%) and dermatologists (70%) for AD. Nonsedating antihistamines accounted for the majority of the antihistamines prescribed by family physicians (84%), internists (100%), and other specialists (55%), the investigators said.
(The sedating antihistamines prescribed included hydroxyzine, diphenhydramine, chlorpheniramine, brompheniramine, and cyproheptadine; nonsedating antihistamines include cetirizine, desloratadine, levocetirizine, loratadine, and fexofenadine.)
Although the AAD guidelines allow intermittent, short-term use of sedating antihistamines to treat AD-associated itch, these medications may be harmful to sleep in terms of reduced sleep quality and decreased REM sleep. Also, studies have shown that their effects can persist into the daytime and have the potential to impair cognitive function, including learning and memory.
“Physicians should consider the potential risks when prescribing sedating antihistamines as adjunctive treatment for atopic dermatitis,” Dr. He and her associates warned in the article in the Journal of the American Academy of Dermatology.
The researchers took a look at the top ten comorbidities reported among visits for AD, because nonsedating antihistamines might have been prescribed for a different diagnosis. There were three conditions for which antihistamines may be indicated: allergic rhinitis (13%), dermatitis attributable to food (8.5%), and conjunctivitis (3%). This “validates antihistamine prescriptions for a maximum of only 24.5% of patients who received antihistamines, indicating that a large proportion of antihistamine prescriptions were prescribed specifically for AD,” they said.
The authors said that, “while histamine does not play a role in AD via H1R [histamine-1 receptor], it may still be relevant in AD pathogenesis through actions on its most recently described receptor, histamine-4 receptor (H4R).”
“The advent of new targeted systemic therapies, such as T-helper 2 cytokine antagonists and H4R antagonists,” may one day help fill “the unmet need for effective treatments for atopic dermatitis,” Dr. He and her associates concluded.
The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories. Dr. He listed no other relevant financial disclosures. Her coauthors disclosed research, speaking, and/or consulting support from a variety of pharmaceutical companies; one author is an employee of Abbvie.
SOURCE: He A et al. J Amer Acad of Dermatol. 2008. doi: 10.1016/j.jaad.2017.12.077.
said Alice He, MD, at the Center for Dermatology Research, Wake Forest University, Winston-Salem, N.C., and her associates.
Results of double-blind, randomized trials have found that oral antihistamines do not effectively treat itch associated with atopic dermatitis (AD), and American Academy of Dermatology guidelines state that intermittent short-term use of sedating antihistamines may help insomnia secondary to itch, but should not be substituted for topical treatments in atopic dermatitis management (J Am Acad Dermatol. 2014;71[2]:327-49), the investigators said. Nonetheless, physicians continue to prescribe antihistamines to AD patients.
Sedating antihistamines accounted for the majority of antihistamines prescribed by pediatricians (58%) and dermatologists (70%) for AD. Nonsedating antihistamines accounted for the majority of the antihistamines prescribed by family physicians (84%), internists (100%), and other specialists (55%), the investigators said.
(The sedating antihistamines prescribed included hydroxyzine, diphenhydramine, chlorpheniramine, brompheniramine, and cyproheptadine; nonsedating antihistamines include cetirizine, desloratadine, levocetirizine, loratadine, and fexofenadine.)
Although the AAD guidelines allow intermittent, short-term use of sedating antihistamines to treat AD-associated itch, these medications may be harmful to sleep in terms of reduced sleep quality and decreased REM sleep. Also, studies have shown that their effects can persist into the daytime and have the potential to impair cognitive function, including learning and memory.
“Physicians should consider the potential risks when prescribing sedating antihistamines as adjunctive treatment for atopic dermatitis,” Dr. He and her associates warned in the article in the Journal of the American Academy of Dermatology.
The researchers took a look at the top ten comorbidities reported among visits for AD, because nonsedating antihistamines might have been prescribed for a different diagnosis. There were three conditions for which antihistamines may be indicated: allergic rhinitis (13%), dermatitis attributable to food (8.5%), and conjunctivitis (3%). This “validates antihistamine prescriptions for a maximum of only 24.5% of patients who received antihistamines, indicating that a large proportion of antihistamine prescriptions were prescribed specifically for AD,” they said.
The authors said that, “while histamine does not play a role in AD via H1R [histamine-1 receptor], it may still be relevant in AD pathogenesis through actions on its most recently described receptor, histamine-4 receptor (H4R).”
“The advent of new targeted systemic therapies, such as T-helper 2 cytokine antagonists and H4R antagonists,” may one day help fill “the unmet need for effective treatments for atopic dermatitis,” Dr. He and her associates concluded.
The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories. Dr. He listed no other relevant financial disclosures. Her coauthors disclosed research, speaking, and/or consulting support from a variety of pharmaceutical companies; one author is an employee of Abbvie.
SOURCE: He A et al. J Amer Acad of Dermatol. 2008. doi: 10.1016/j.jaad.2017.12.077.
FROM JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point: Physicians should consider the potential risks when prescribing sedating antihistamines as adjunctive treatment for atopic dermatitis.
Major finding: Physicians from specialties other than dermatology prescribed antihistamines at a greater proportion of AD visits than dermatologists (26%-44% of visits vs. 22%), with the exception of pediatricians (16%).
Study details: Data from the National Ambulatory Medical Care Survey on 9.9 million physician visits for AD from 2003 to 2012.
Disclosures: The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories. Dr. He listed no other relevant financial disclosures. Her associates disclosed research, speaking and/or consulting support from a variety of pharmaceutical companies. One author was an employee of Abbvie.
Source: He A et al. J Amer Acad of Dermatol. 2008. doi: 10.1016/j.jaad.2017.12.077.
Doctors to Congress: Keep Part B drug payments out of MIPS adjustment
Physician specialists are calling on Congress to isolate Medicare Part B drug reimbursements from payment adjustments under the Merit-Based Incentive Payment System (MIPS).
A coalition of medical societies, large group practices, and patient advocacy groups has asked for an “intervention this year with a technical correction that ensures the [MIPS] score adjustment is not applied to Part B drug payments,” according to Jan. 18 letter sent to the leaders of the Senate Finance Committee, House Energy and Commerce Committee, and the House Ways and Means Committee. “Since the 2018 MIPS year has begun, it is imperative that Congress acts quickly to ensure that patient access to critical treatments is not negatively impacted.”
Under MIPS, physicians are scored based on their performance across three categories: quality, improvement activities, and advancing care information. A fourth category, cost, is planned but not yet included in the score (although cost doesn’t impact adjustments until 2020, it is part of the 2018 program year). Medicare payments, which currently include Part B drug reimbursements, are subject to bonuses and penalties based on performance scores.
In their November 2017 update to the Quality Payment Program, which includes MIPS, officials at the Centers for Medicare & Medicaid Services said they would be moving forward with including Part B drug payments in the MIPS adjustment.
“This application of the adjustment ... is a significant departure from current policy and would disproportionately affect certain specialties,” according to the coalition’s letter.
Certain specialties, including rheumatology, oncology, and ophthalmology, have more to lose under the current policy because these specialists administer more Part B drugs than other specialists, according to health care consultancy Avalere Health.
For gastroenterologists, the primary concern with the application of the MIPS payment adjustment to Part B drugs is patient access to the biologics and biosimilars used to treat irritable bowel disease including Crohn’s disease and ulcerative colitis. Under CMS’s policy, gastroenterologists facing a penalty or negative payment adjustment may have Part B drug payments fall below what it costs to buy the Part B drug. Since Medicare payment for Part B drugs is based on average sales price (ASP), affected practices are more likely to be small, have a smaller number of patients on a Part B drug or prescribe a broader range of Part B drugs to patients. As MIPS payment adjustments increase each year the impact of the policy is expected to touch more practices and bring larger deficits further eroding access to the biologics and biosimilars used to treat inflammatory bowel disease.
“Certain specialists administer more Part B drugs than others and, therefore, may be exposed to significant financial risk and payment swings year-over-year under the CMS [Centers for Medicare & Medicaid Services] proposal,” John Feore, director at Avalere, said in a statement.
In 2018, physicians in those specialties could see drug payments increase or decrease by as much as 16%, according to Avalere research.
The policy likely will have an even greater effect on smaller practices and those in rural settings and could lead to access issues, according to the coalition letter.
“Some patients already face access challenges because the budget sequester has eroded reimbursements to physicians, and this policy would exacerbate these problems,” the letter states. “Patients would be left with fewer locations where they could receive care, resulting in less access and higher costs. A growing number of patients would then have to seek care in a hospital, which would result in higher out-of-pocket expenses and, particularly in rural communities, may require traveling longer distances to receive care.”
Physician specialists are calling on Congress to isolate Medicare Part B drug reimbursements from payment adjustments under the Merit-Based Incentive Payment System (MIPS).
A coalition of medical societies, large group practices, and patient advocacy groups has asked for an “intervention this year with a technical correction that ensures the [MIPS] score adjustment is not applied to Part B drug payments,” according to Jan. 18 letter sent to the leaders of the Senate Finance Committee, House Energy and Commerce Committee, and the House Ways and Means Committee. “Since the 2018 MIPS year has begun, it is imperative that Congress acts quickly to ensure that patient access to critical treatments is not negatively impacted.”
Under MIPS, physicians are scored based on their performance across three categories: quality, improvement activities, and advancing care information. A fourth category, cost, is planned but not yet included in the score (although cost doesn’t impact adjustments until 2020, it is part of the 2018 program year). Medicare payments, which currently include Part B drug reimbursements, are subject to bonuses and penalties based on performance scores.
In their November 2017 update to the Quality Payment Program, which includes MIPS, officials at the Centers for Medicare & Medicaid Services said they would be moving forward with including Part B drug payments in the MIPS adjustment.
“This application of the adjustment ... is a significant departure from current policy and would disproportionately affect certain specialties,” according to the coalition’s letter.
Certain specialties, including rheumatology, oncology, and ophthalmology, have more to lose under the current policy because these specialists administer more Part B drugs than other specialists, according to health care consultancy Avalere Health.
For gastroenterologists, the primary concern with the application of the MIPS payment adjustment to Part B drugs is patient access to the biologics and biosimilars used to treat irritable bowel disease including Crohn’s disease and ulcerative colitis. Under CMS’s policy, gastroenterologists facing a penalty or negative payment adjustment may have Part B drug payments fall below what it costs to buy the Part B drug. Since Medicare payment for Part B drugs is based on average sales price (ASP), affected practices are more likely to be small, have a smaller number of patients on a Part B drug or prescribe a broader range of Part B drugs to patients. As MIPS payment adjustments increase each year the impact of the policy is expected to touch more practices and bring larger deficits further eroding access to the biologics and biosimilars used to treat inflammatory bowel disease.
“Certain specialists administer more Part B drugs than others and, therefore, may be exposed to significant financial risk and payment swings year-over-year under the CMS [Centers for Medicare & Medicaid Services] proposal,” John Feore, director at Avalere, said in a statement.
In 2018, physicians in those specialties could see drug payments increase or decrease by as much as 16%, according to Avalere research.
The policy likely will have an even greater effect on smaller practices and those in rural settings and could lead to access issues, according to the coalition letter.
“Some patients already face access challenges because the budget sequester has eroded reimbursements to physicians, and this policy would exacerbate these problems,” the letter states. “Patients would be left with fewer locations where they could receive care, resulting in less access and higher costs. A growing number of patients would then have to seek care in a hospital, which would result in higher out-of-pocket expenses and, particularly in rural communities, may require traveling longer distances to receive care.”
Physician specialists are calling on Congress to isolate Medicare Part B drug reimbursements from payment adjustments under the Merit-Based Incentive Payment System (MIPS).
A coalition of medical societies, large group practices, and patient advocacy groups has asked for an “intervention this year with a technical correction that ensures the [MIPS] score adjustment is not applied to Part B drug payments,” according to Jan. 18 letter sent to the leaders of the Senate Finance Committee, House Energy and Commerce Committee, and the House Ways and Means Committee. “Since the 2018 MIPS year has begun, it is imperative that Congress acts quickly to ensure that patient access to critical treatments is not negatively impacted.”
Under MIPS, physicians are scored based on their performance across three categories: quality, improvement activities, and advancing care information. A fourth category, cost, is planned but not yet included in the score (although cost doesn’t impact adjustments until 2020, it is part of the 2018 program year). Medicare payments, which currently include Part B drug reimbursements, are subject to bonuses and penalties based on performance scores.
In their November 2017 update to the Quality Payment Program, which includes MIPS, officials at the Centers for Medicare & Medicaid Services said they would be moving forward with including Part B drug payments in the MIPS adjustment.
“This application of the adjustment ... is a significant departure from current policy and would disproportionately affect certain specialties,” according to the coalition’s letter.
Certain specialties, including rheumatology, oncology, and ophthalmology, have more to lose under the current policy because these specialists administer more Part B drugs than other specialists, according to health care consultancy Avalere Health.
For gastroenterologists, the primary concern with the application of the MIPS payment adjustment to Part B drugs is patient access to the biologics and biosimilars used to treat irritable bowel disease including Crohn’s disease and ulcerative colitis. Under CMS’s policy, gastroenterologists facing a penalty or negative payment adjustment may have Part B drug payments fall below what it costs to buy the Part B drug. Since Medicare payment for Part B drugs is based on average sales price (ASP), affected practices are more likely to be small, have a smaller number of patients on a Part B drug or prescribe a broader range of Part B drugs to patients. As MIPS payment adjustments increase each year the impact of the policy is expected to touch more practices and bring larger deficits further eroding access to the biologics and biosimilars used to treat inflammatory bowel disease.
“Certain specialists administer more Part B drugs than others and, therefore, may be exposed to significant financial risk and payment swings year-over-year under the CMS [Centers for Medicare & Medicaid Services] proposal,” John Feore, director at Avalere, said in a statement.
In 2018, physicians in those specialties could see drug payments increase or decrease by as much as 16%, according to Avalere research.
The policy likely will have an even greater effect on smaller practices and those in rural settings and could lead to access issues, according to the coalition letter.
“Some patients already face access challenges because the budget sequester has eroded reimbursements to physicians, and this policy would exacerbate these problems,” the letter states. “Patients would be left with fewer locations where they could receive care, resulting in less access and higher costs. A growing number of patients would then have to seek care in a hospital, which would result in higher out-of-pocket expenses and, particularly in rural communities, may require traveling longer distances to receive care.”
Genetic Screens Yield Potential Therapies for Neurodegenerative Diseases
SAN DIEGO—Cross-species genetic screens are helping researchers find molecules that modulate the proteins that cause adult neurodegenerative disease, according to a lecture delivered at the 142nd Annual Meeting of the American Neurological Association. Such screening thus reveals potential therapeutic targets and augments scientific understanding of the biology of these proteins.
The research raises the possibility that clinicians will be able to delay or prevent neurodegenerative disease in the future through the early administration of molecules that target these proteins. “We need to identify those at risk and begin the therapy … before the symptoms develop, just like you would treat somebody with statins if they have high cholesterol before they have a heart attack,” said Huda Y. Zoghbi, MD, an investigator with the Howard Hughes Medical Institute; Professor of Pediatrics, Molecular and Human Genetics, Neuroscience, and Neurology at Baylor College of Medicine; and Director of the Jan and Dan Duncan Neurological Research Institute in Houston.
Research Into a Rare Disorder
Studying the rare disorder spinocerebellar ataxia type 1 (SCA1) has yielded information that could be applicable to more common neurodegenerative diseases, said Dr. Zoghbi. SCA1 is characterized by a loss of Purkinje cells and brainstem neurons that impairs balance and coordination and increases the risk of premature death. In 1993, Dr. Zoghbi; Harry Orr, PhD, Professor and Tulloch Chair in Genetics at the University of Minnesota in Minneapolis; and colleagues discovered that a CAG repeat expansion in ATXN1 causes SCA1 by producing an abnormally long version of the ataxin-1 protein. They also found that neurodegeneration results if levels of normal ataxin-1 are increased by 20% or 30%. The brain thus is highly sensitive to ataxin-1 levels, said Dr. Zoghbi.
Borrowing a technique from cancer research, the investigators performed genetic screening using fruit fly and human cells to find targets that would reduce ataxin-1 levels when inhibited. They found approximately 30 relevant genes in each organism, and about 12 were common to both organisms. All of the shared genes operate in the mitogen-activated protein (MAP) kinase pathway, and inhibiting each gene lowered ataxin-1 in cells and flies.
Inhibiting Enzymes
The researchers also observed that the enzymes MSK1 and MSK2 intervene in the pathway and promote ataxin-1 accumulation. Inhibiting MSK1 produced clinical improvement in SCA1 mouse models, and inhibiting MSK1 and MSK2 together produced still more improvement. A small molecule that inhibited MSK1 therefore could help patients with SCA1, said Dr. Zoghbi.
Inhibiting enzymes such as MSK1 and MSK2 for years at a time could raise safety concerns, however. The investigators thus decided to look for other modulators of ataxin-1, on the theory that targeting modulators that function in different pathways could reduce the amount of inhibition required and decrease the risk of adverse events.
Further screening revealed that PKA1 appeared to modulate ataxin-1 by a mechanism similar to that of MSK1. An animal study indicated that inhibiting MSK1 and inhibiting PKA1 produced equivalent reductions on ataxin-1, but that inhibiting both in tandem yielded a greater reduction. The investigators then found that the PAK1 enzyme promoted ataxin-1 accumulation through a pathway different from that of MSK1 and PKA1. Inhibiting PAK1 reduced ataxin-1 levels, and inhibiting PAK1 and MSK1 simultaneously had a still greater effect.
Targeting Tauopathies
Their research into kinases and enzymes prompted Dr. Zoghbi and colleagues to consider whole genome screening as a method of targeting proteins that cause neurodegenerative diseases other than SCA1. Overexpression of tau, for example, causes neurodegeneration, regardless of whether the overexpression results from a mutation in tau-encoding genes. “Tau is a true culprit in dementias, and we thought that if we could find something to lower it, we could help patients with these disorders,” said Dr. Zoghbi.
Another genetic screen suggested that the enzyme Nuak1 stabilizes tau by phosphorylating it at Ser356. The investigators observed that inhibiting Nuak1 reduced tau levels and suppressed neurodegeneration in human cells and in fruit flies. Tau accumulation decreases fruit flies’ climbing ability, and inhibiting Nuak1 improved this ability in flies with tau accumulation.
In a subsequent mouse study, Dr. Zoghbi and colleagues found that inhibiting Nuak1 significantly reduced levels of phosphorylated tau and provided smaller reductions in total tau and endogenous tau. They also observed that mice with tauopathy took longer than wild-type mice to complete a water maze task. Inhibiting Nuak1 in mice with tauopathy improved their performance on this task. Nuak1 inhibition also restored synaptic plasticity in these mice to a level similar to that of wild-type mice. Finally, Nuak1 inhibition reduced tau tangle pathology and increased survival. Dr. Zoghbi and colleagues are now searching for small-molecule Nuak1 inhibitors that could provide protection against tauopathy.
In Search of More Targets
The investigators next looked for genes that influence tau. Successive levels of genetic screening identified 59 genes that “robustly lower tau levels,” said Dr. Zoghbi. She and her colleagues prioritized 12 of the genes for investigation.
They used adenoassociated viral vectors to deliver therapies that can knock out mouse genes for as long as a year. With this technique, the investigators confirmed that all of the initial 12 genes decreased tau levels. In principle, this strategy could enable researchers to scan the whole genome for genes that modulate tau, said Dr. Zoghbi.
—Erik Greb
Suggested Reading
Lasagna-Reeves CA, de Haro M, Hao S, et al. Reduction of Nuak1 decreases tau and reverses phenotypes in a tauopathy mouse model. Neuron. 2016; 92(2):407-418.
Park J, Al-Ramahi I, Tan Q, et al. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013;498(7454):325-331.
Rousseaux MW, de Haro M, Lasagna-Reeves CA, et al. TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. Elife. 2016 Oct 25;5. pii: e19809
SAN DIEGO—Cross-species genetic screens are helping researchers find molecules that modulate the proteins that cause adult neurodegenerative disease, according to a lecture delivered at the 142nd Annual Meeting of the American Neurological Association. Such screening thus reveals potential therapeutic targets and augments scientific understanding of the biology of these proteins.
The research raises the possibility that clinicians will be able to delay or prevent neurodegenerative disease in the future through the early administration of molecules that target these proteins. “We need to identify those at risk and begin the therapy … before the symptoms develop, just like you would treat somebody with statins if they have high cholesterol before they have a heart attack,” said Huda Y. Zoghbi, MD, an investigator with the Howard Hughes Medical Institute; Professor of Pediatrics, Molecular and Human Genetics, Neuroscience, and Neurology at Baylor College of Medicine; and Director of the Jan and Dan Duncan Neurological Research Institute in Houston.
Research Into a Rare Disorder
Studying the rare disorder spinocerebellar ataxia type 1 (SCA1) has yielded information that could be applicable to more common neurodegenerative diseases, said Dr. Zoghbi. SCA1 is characterized by a loss of Purkinje cells and brainstem neurons that impairs balance and coordination and increases the risk of premature death. In 1993, Dr. Zoghbi; Harry Orr, PhD, Professor and Tulloch Chair in Genetics at the University of Minnesota in Minneapolis; and colleagues discovered that a CAG repeat expansion in ATXN1 causes SCA1 by producing an abnormally long version of the ataxin-1 protein. They also found that neurodegeneration results if levels of normal ataxin-1 are increased by 20% or 30%. The brain thus is highly sensitive to ataxin-1 levels, said Dr. Zoghbi.
Borrowing a technique from cancer research, the investigators performed genetic screening using fruit fly and human cells to find targets that would reduce ataxin-1 levels when inhibited. They found approximately 30 relevant genes in each organism, and about 12 were common to both organisms. All of the shared genes operate in the mitogen-activated protein (MAP) kinase pathway, and inhibiting each gene lowered ataxin-1 in cells and flies.
Inhibiting Enzymes
The researchers also observed that the enzymes MSK1 and MSK2 intervene in the pathway and promote ataxin-1 accumulation. Inhibiting MSK1 produced clinical improvement in SCA1 mouse models, and inhibiting MSK1 and MSK2 together produced still more improvement. A small molecule that inhibited MSK1 therefore could help patients with SCA1, said Dr. Zoghbi.
Inhibiting enzymes such as MSK1 and MSK2 for years at a time could raise safety concerns, however. The investigators thus decided to look for other modulators of ataxin-1, on the theory that targeting modulators that function in different pathways could reduce the amount of inhibition required and decrease the risk of adverse events.
Further screening revealed that PKA1 appeared to modulate ataxin-1 by a mechanism similar to that of MSK1. An animal study indicated that inhibiting MSK1 and inhibiting PKA1 produced equivalent reductions on ataxin-1, but that inhibiting both in tandem yielded a greater reduction. The investigators then found that the PAK1 enzyme promoted ataxin-1 accumulation through a pathway different from that of MSK1 and PKA1. Inhibiting PAK1 reduced ataxin-1 levels, and inhibiting PAK1 and MSK1 simultaneously had a still greater effect.
Targeting Tauopathies
Their research into kinases and enzymes prompted Dr. Zoghbi and colleagues to consider whole genome screening as a method of targeting proteins that cause neurodegenerative diseases other than SCA1. Overexpression of tau, for example, causes neurodegeneration, regardless of whether the overexpression results from a mutation in tau-encoding genes. “Tau is a true culprit in dementias, and we thought that if we could find something to lower it, we could help patients with these disorders,” said Dr. Zoghbi.
Another genetic screen suggested that the enzyme Nuak1 stabilizes tau by phosphorylating it at Ser356. The investigators observed that inhibiting Nuak1 reduced tau levels and suppressed neurodegeneration in human cells and in fruit flies. Tau accumulation decreases fruit flies’ climbing ability, and inhibiting Nuak1 improved this ability in flies with tau accumulation.
In a subsequent mouse study, Dr. Zoghbi and colleagues found that inhibiting Nuak1 significantly reduced levels of phosphorylated tau and provided smaller reductions in total tau and endogenous tau. They also observed that mice with tauopathy took longer than wild-type mice to complete a water maze task. Inhibiting Nuak1 in mice with tauopathy improved their performance on this task. Nuak1 inhibition also restored synaptic plasticity in these mice to a level similar to that of wild-type mice. Finally, Nuak1 inhibition reduced tau tangle pathology and increased survival. Dr. Zoghbi and colleagues are now searching for small-molecule Nuak1 inhibitors that could provide protection against tauopathy.
In Search of More Targets
The investigators next looked for genes that influence tau. Successive levels of genetic screening identified 59 genes that “robustly lower tau levels,” said Dr. Zoghbi. She and her colleagues prioritized 12 of the genes for investigation.
They used adenoassociated viral vectors to deliver therapies that can knock out mouse genes for as long as a year. With this technique, the investigators confirmed that all of the initial 12 genes decreased tau levels. In principle, this strategy could enable researchers to scan the whole genome for genes that modulate tau, said Dr. Zoghbi.
—Erik Greb
Suggested Reading
Lasagna-Reeves CA, de Haro M, Hao S, et al. Reduction of Nuak1 decreases tau and reverses phenotypes in a tauopathy mouse model. Neuron. 2016; 92(2):407-418.
Park J, Al-Ramahi I, Tan Q, et al. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013;498(7454):325-331.
Rousseaux MW, de Haro M, Lasagna-Reeves CA, et al. TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. Elife. 2016 Oct 25;5. pii: e19809
SAN DIEGO—Cross-species genetic screens are helping researchers find molecules that modulate the proteins that cause adult neurodegenerative disease, according to a lecture delivered at the 142nd Annual Meeting of the American Neurological Association. Such screening thus reveals potential therapeutic targets and augments scientific understanding of the biology of these proteins.
The research raises the possibility that clinicians will be able to delay or prevent neurodegenerative disease in the future through the early administration of molecules that target these proteins. “We need to identify those at risk and begin the therapy … before the symptoms develop, just like you would treat somebody with statins if they have high cholesterol before they have a heart attack,” said Huda Y. Zoghbi, MD, an investigator with the Howard Hughes Medical Institute; Professor of Pediatrics, Molecular and Human Genetics, Neuroscience, and Neurology at Baylor College of Medicine; and Director of the Jan and Dan Duncan Neurological Research Institute in Houston.
Research Into a Rare Disorder
Studying the rare disorder spinocerebellar ataxia type 1 (SCA1) has yielded information that could be applicable to more common neurodegenerative diseases, said Dr. Zoghbi. SCA1 is characterized by a loss of Purkinje cells and brainstem neurons that impairs balance and coordination and increases the risk of premature death. In 1993, Dr. Zoghbi; Harry Orr, PhD, Professor and Tulloch Chair in Genetics at the University of Minnesota in Minneapolis; and colleagues discovered that a CAG repeat expansion in ATXN1 causes SCA1 by producing an abnormally long version of the ataxin-1 protein. They also found that neurodegeneration results if levels of normal ataxin-1 are increased by 20% or 30%. The brain thus is highly sensitive to ataxin-1 levels, said Dr. Zoghbi.
Borrowing a technique from cancer research, the investigators performed genetic screening using fruit fly and human cells to find targets that would reduce ataxin-1 levels when inhibited. They found approximately 30 relevant genes in each organism, and about 12 were common to both organisms. All of the shared genes operate in the mitogen-activated protein (MAP) kinase pathway, and inhibiting each gene lowered ataxin-1 in cells and flies.
Inhibiting Enzymes
The researchers also observed that the enzymes MSK1 and MSK2 intervene in the pathway and promote ataxin-1 accumulation. Inhibiting MSK1 produced clinical improvement in SCA1 mouse models, and inhibiting MSK1 and MSK2 together produced still more improvement. A small molecule that inhibited MSK1 therefore could help patients with SCA1, said Dr. Zoghbi.
Inhibiting enzymes such as MSK1 and MSK2 for years at a time could raise safety concerns, however. The investigators thus decided to look for other modulators of ataxin-1, on the theory that targeting modulators that function in different pathways could reduce the amount of inhibition required and decrease the risk of adverse events.
Further screening revealed that PKA1 appeared to modulate ataxin-1 by a mechanism similar to that of MSK1. An animal study indicated that inhibiting MSK1 and inhibiting PKA1 produced equivalent reductions on ataxin-1, but that inhibiting both in tandem yielded a greater reduction. The investigators then found that the PAK1 enzyme promoted ataxin-1 accumulation through a pathway different from that of MSK1 and PKA1. Inhibiting PAK1 reduced ataxin-1 levels, and inhibiting PAK1 and MSK1 simultaneously had a still greater effect.
Targeting Tauopathies
Their research into kinases and enzymes prompted Dr. Zoghbi and colleagues to consider whole genome screening as a method of targeting proteins that cause neurodegenerative diseases other than SCA1. Overexpression of tau, for example, causes neurodegeneration, regardless of whether the overexpression results from a mutation in tau-encoding genes. “Tau is a true culprit in dementias, and we thought that if we could find something to lower it, we could help patients with these disorders,” said Dr. Zoghbi.
Another genetic screen suggested that the enzyme Nuak1 stabilizes tau by phosphorylating it at Ser356. The investigators observed that inhibiting Nuak1 reduced tau levels and suppressed neurodegeneration in human cells and in fruit flies. Tau accumulation decreases fruit flies’ climbing ability, and inhibiting Nuak1 improved this ability in flies with tau accumulation.
In a subsequent mouse study, Dr. Zoghbi and colleagues found that inhibiting Nuak1 significantly reduced levels of phosphorylated tau and provided smaller reductions in total tau and endogenous tau. They also observed that mice with tauopathy took longer than wild-type mice to complete a water maze task. Inhibiting Nuak1 in mice with tauopathy improved their performance on this task. Nuak1 inhibition also restored synaptic plasticity in these mice to a level similar to that of wild-type mice. Finally, Nuak1 inhibition reduced tau tangle pathology and increased survival. Dr. Zoghbi and colleagues are now searching for small-molecule Nuak1 inhibitors that could provide protection against tauopathy.
In Search of More Targets
The investigators next looked for genes that influence tau. Successive levels of genetic screening identified 59 genes that “robustly lower tau levels,” said Dr. Zoghbi. She and her colleagues prioritized 12 of the genes for investigation.
They used adenoassociated viral vectors to deliver therapies that can knock out mouse genes for as long as a year. With this technique, the investigators confirmed that all of the initial 12 genes decreased tau levels. In principle, this strategy could enable researchers to scan the whole genome for genes that modulate tau, said Dr. Zoghbi.
—Erik Greb
Suggested Reading
Lasagna-Reeves CA, de Haro M, Hao S, et al. Reduction of Nuak1 decreases tau and reverses phenotypes in a tauopathy mouse model. Neuron. 2016; 92(2):407-418.
Park J, Al-Ramahi I, Tan Q, et al. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013;498(7454):325-331.
Rousseaux MW, de Haro M, Lasagna-Reeves CA, et al. TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. Elife. 2016 Oct 25;5. pii: e19809
Ibudilast shows promise in progressive MS
San Diego – In a phase 2 trial, .
“That was a striking result,” one of the study authors, Robert T. Naismith, MD, said in an interview prior to presenting the study at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We’ll need to see how that translates into a possible clinical benefit.”
In a trial known as SPRINT-MS/NN 102, researchers led by principal investigator Robert Fox, MD, a neurologist at the Cleveland Clinic in Ohio, along with colleagues in the NeuroNEXT Network, randomized 255 subjects with primary or secondary progressive MS to receive either ibudilast up to 100 mg/day (50 mg twice daily) or matching placebo and followed them for 96 weeks. They assessed clinical and imaging outcomes every 24 weeks, and the primary outcome was change in brain atrophy as measured by brain parenchymal fraction (BPF) over 96 weeks. Secondary outcomes included magnetization transfer ratio (MTR), diffusion tensor imaging, and optical coherence tomography. Analysis was based on a modified intention-to-treat approach, and linear mixed effects modeling was used to estimate the rate of change within imaging measures for each treatment group.
The 255 subjects were enrolled at 28 U.S. sites and their last follow-up visit was completed on May 11, 2017. The retention rate through week 96 was 86%, or 219 patients. The researchers found that treatment with ibudilast was associated with a 48% slowing in the rate of decline in brain atrophy as measured by BPF. A per-protocol analysis yielded similar results (P = .045). In addition, no increased rate of serious adverse events and no opportunistic infections or cancer signals were observed. As for tolerability, 25% of subjects on placebo and 30% of those on ibudilast discontinued treatment (P = .30). The main treatment-related adverse events were gastrointestinal in nature (20% in the placebo group vs. 67% in the ibudilast group; P = .002), primarily nausea.
In the analysis of key secondary outcomes, the researchers found that the change in MTR in normal-appearing brain tissue was reduced –0.00558 for ibudilast and –0.03064 for placebo, which was a relative reduction of 82% in MTR decline. At the same time, the change in MTR in normal-appearing gray matter was reduced –0.00753 for ibudilast and –0.03210 for placebo, which was a relative reduction of 77% in MTR decline. No significant difference in white matter changes were observed in transverse diffusivity (P = .15) or longitudinal diffusivity (P = .73), compared with placebo.
For the secondary endpoint of disability, a blinded evaluator assessed Expanded Disability Status Scale (EDSS) score at baseline and every 24 weeks. The researchers used a time-to-event Kaplan-Meier analysis and a Cox proportional hazards model to determine time to confirmed EDSS progression not due to relapse. They found that the hazard ratio for progression in the ibudilast group, compared with the placebo group, was 0.74, with a 90% confidence interval of 0.47-1.17 (P = .29).
“Ibudilast is a novel therapy for progressive MS, with a positive phase 2 study,” Dr. Naismith concluded. “Safety and tolerability were favorable. Clinical endpoints from this trial will be forthcoming.”
The NeuroNEXT Network is supported by the National Institute of Neurological Disorders and Stroke. Dr. Naismith reported having no financial disclosures.
SOURCE: Naismith R et al. ACTRIMS Forum 2018 Abstract P029.
San Diego – In a phase 2 trial, .
“That was a striking result,” one of the study authors, Robert T. Naismith, MD, said in an interview prior to presenting the study at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We’ll need to see how that translates into a possible clinical benefit.”
In a trial known as SPRINT-MS/NN 102, researchers led by principal investigator Robert Fox, MD, a neurologist at the Cleveland Clinic in Ohio, along with colleagues in the NeuroNEXT Network, randomized 255 subjects with primary or secondary progressive MS to receive either ibudilast up to 100 mg/day (50 mg twice daily) or matching placebo and followed them for 96 weeks. They assessed clinical and imaging outcomes every 24 weeks, and the primary outcome was change in brain atrophy as measured by brain parenchymal fraction (BPF) over 96 weeks. Secondary outcomes included magnetization transfer ratio (MTR), diffusion tensor imaging, and optical coherence tomography. Analysis was based on a modified intention-to-treat approach, and linear mixed effects modeling was used to estimate the rate of change within imaging measures for each treatment group.
The 255 subjects were enrolled at 28 U.S. sites and their last follow-up visit was completed on May 11, 2017. The retention rate through week 96 was 86%, or 219 patients. The researchers found that treatment with ibudilast was associated with a 48% slowing in the rate of decline in brain atrophy as measured by BPF. A per-protocol analysis yielded similar results (P = .045). In addition, no increased rate of serious adverse events and no opportunistic infections or cancer signals were observed. As for tolerability, 25% of subjects on placebo and 30% of those on ibudilast discontinued treatment (P = .30). The main treatment-related adverse events were gastrointestinal in nature (20% in the placebo group vs. 67% in the ibudilast group; P = .002), primarily nausea.
In the analysis of key secondary outcomes, the researchers found that the change in MTR in normal-appearing brain tissue was reduced –0.00558 for ibudilast and –0.03064 for placebo, which was a relative reduction of 82% in MTR decline. At the same time, the change in MTR in normal-appearing gray matter was reduced –0.00753 for ibudilast and –0.03210 for placebo, which was a relative reduction of 77% in MTR decline. No significant difference in white matter changes were observed in transverse diffusivity (P = .15) or longitudinal diffusivity (P = .73), compared with placebo.
For the secondary endpoint of disability, a blinded evaluator assessed Expanded Disability Status Scale (EDSS) score at baseline and every 24 weeks. The researchers used a time-to-event Kaplan-Meier analysis and a Cox proportional hazards model to determine time to confirmed EDSS progression not due to relapse. They found that the hazard ratio for progression in the ibudilast group, compared with the placebo group, was 0.74, with a 90% confidence interval of 0.47-1.17 (P = .29).
“Ibudilast is a novel therapy for progressive MS, with a positive phase 2 study,” Dr. Naismith concluded. “Safety and tolerability were favorable. Clinical endpoints from this trial will be forthcoming.”
The NeuroNEXT Network is supported by the National Institute of Neurological Disorders and Stroke. Dr. Naismith reported having no financial disclosures.
SOURCE: Naismith R et al. ACTRIMS Forum 2018 Abstract P029.
San Diego – In a phase 2 trial, .
“That was a striking result,” one of the study authors, Robert T. Naismith, MD, said in an interview prior to presenting the study at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We’ll need to see how that translates into a possible clinical benefit.”
In a trial known as SPRINT-MS/NN 102, researchers led by principal investigator Robert Fox, MD, a neurologist at the Cleveland Clinic in Ohio, along with colleagues in the NeuroNEXT Network, randomized 255 subjects with primary or secondary progressive MS to receive either ibudilast up to 100 mg/day (50 mg twice daily) or matching placebo and followed them for 96 weeks. They assessed clinical and imaging outcomes every 24 weeks, and the primary outcome was change in brain atrophy as measured by brain parenchymal fraction (BPF) over 96 weeks. Secondary outcomes included magnetization transfer ratio (MTR), diffusion tensor imaging, and optical coherence tomography. Analysis was based on a modified intention-to-treat approach, and linear mixed effects modeling was used to estimate the rate of change within imaging measures for each treatment group.
The 255 subjects were enrolled at 28 U.S. sites and their last follow-up visit was completed on May 11, 2017. The retention rate through week 96 was 86%, or 219 patients. The researchers found that treatment with ibudilast was associated with a 48% slowing in the rate of decline in brain atrophy as measured by BPF. A per-protocol analysis yielded similar results (P = .045). In addition, no increased rate of serious adverse events and no opportunistic infections or cancer signals were observed. As for tolerability, 25% of subjects on placebo and 30% of those on ibudilast discontinued treatment (P = .30). The main treatment-related adverse events were gastrointestinal in nature (20% in the placebo group vs. 67% in the ibudilast group; P = .002), primarily nausea.
In the analysis of key secondary outcomes, the researchers found that the change in MTR in normal-appearing brain tissue was reduced –0.00558 for ibudilast and –0.03064 for placebo, which was a relative reduction of 82% in MTR decline. At the same time, the change in MTR in normal-appearing gray matter was reduced –0.00753 for ibudilast and –0.03210 for placebo, which was a relative reduction of 77% in MTR decline. No significant difference in white matter changes were observed in transverse diffusivity (P = .15) or longitudinal diffusivity (P = .73), compared with placebo.
For the secondary endpoint of disability, a blinded evaluator assessed Expanded Disability Status Scale (EDSS) score at baseline and every 24 weeks. The researchers used a time-to-event Kaplan-Meier analysis and a Cox proportional hazards model to determine time to confirmed EDSS progression not due to relapse. They found that the hazard ratio for progression in the ibudilast group, compared with the placebo group, was 0.74, with a 90% confidence interval of 0.47-1.17 (P = .29).
“Ibudilast is a novel therapy for progressive MS, with a positive phase 2 study,” Dr. Naismith concluded. “Safety and tolerability were favorable. Clinical endpoints from this trial will be forthcoming.”
The NeuroNEXT Network is supported by the National Institute of Neurological Disorders and Stroke. Dr. Naismith reported having no financial disclosures.
SOURCE: Naismith R et al. ACTRIMS Forum 2018 Abstract P029.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Ibudilast’s positive phase 2 trial results in progressive multiple sclerosis patients bode well for future development.
Major finding: Ibudilast treatment was associated with a 48% slowing in the rate of decline in brain atrophy as measured by brain parenchymal fraction.
Study details: A randomized trial of 255 subjects with progressive MS enrolled at 28 U.S. sites.
Disclosures: The NeuroNEXT Network is supported by the National Institute of Neurological Disorders and Stroke. Dr. Naismith reported having no financial disclosures.
Source: Naismith R et al. ACTRIMS Forum 2018 Abstract P029.
Integrating behavioral health into primary care
This is the sixth in a series of articles from the National Center for Excellence in Primary Care Research in the Agency for Healthcare Research and Quality. This series introduces sets of tools and resources designed to help your practice.
Primary care practice is under increasing pressure to evolve. As highlighted in this series, topics such as shared decision making, team-based care, integration of behavioral health into primary care practice, and practice facilitation all offer the potential to enhance your primary care practice. On the other hand, quality of care must remain a top priority during this transformation. While much of the Agency for Healthcare Research and Quality’s (AHRQ) work in quality of care focuses on the inpatient setting, AHRQ offers many tools and resources to evaluate quality of care and to implement quality improvement into your primary care practice.
The NQMC mission is to provide an accessible mechanism for obtaining detailed information on quality measures and to further the dissemination, implementation, and use of these measures to inform health care decisions. NQMC is designed for practitioners, health care providers, health plans, integrated delivery systems, purchasers, and others interested in health care quality measurement. Funding for the NQMC is in question, and the future of this resource is not certain.
Confidential feedback reporting is widely considered to be a precursor to and a foundation for performance improvement. However, to enable change, the clinician responsible for and capable of change must receive, understand, and act on the information. The following publications from the National Center for Excellence in Primary Care Research offer some guidance from the on ways to best do so:
- Confidential Physician Feedback Reports: Designing for Optimal Impact on Performance is a guide that informs developers of feedback reports about evidence-based strategies to consider when they develop or refine a feedback reporting system.
- Will It Work Here? A Decisionmaker’s Guide to Adopting Innovations can help you determine if an innovation would be a good fit – or an appropriate stretch – for your practice or health care organization by asking a series of questions. It links users to actionable Web-based tools and presents case studies that illustrate how other organizations have addressed these questions.
- Improving Your Office Testing Process: A Toolkit for Rapid-Cycle Patient Safety and Quality Improvement provides information and resources to help physicians’ offices, clinics, and other ambulatory care facilities assess and improve the testing process in their offices.
These and other tools can be found at the AHRQ website.
Dr. Ganiats is the director for the National Center for Excellence in Primary Care Research at AHRQ.
This is the sixth in a series of articles from the National Center for Excellence in Primary Care Research in the Agency for Healthcare Research and Quality. This series introduces sets of tools and resources designed to help your practice.
Primary care practice is under increasing pressure to evolve. As highlighted in this series, topics such as shared decision making, team-based care, integration of behavioral health into primary care practice, and practice facilitation all offer the potential to enhance your primary care practice. On the other hand, quality of care must remain a top priority during this transformation. While much of the Agency for Healthcare Research and Quality’s (AHRQ) work in quality of care focuses on the inpatient setting, AHRQ offers many tools and resources to evaluate quality of care and to implement quality improvement into your primary care practice.
The NQMC mission is to provide an accessible mechanism for obtaining detailed information on quality measures and to further the dissemination, implementation, and use of these measures to inform health care decisions. NQMC is designed for practitioners, health care providers, health plans, integrated delivery systems, purchasers, and others interested in health care quality measurement. Funding for the NQMC is in question, and the future of this resource is not certain.
Confidential feedback reporting is widely considered to be a precursor to and a foundation for performance improvement. However, to enable change, the clinician responsible for and capable of change must receive, understand, and act on the information. The following publications from the National Center for Excellence in Primary Care Research offer some guidance from the on ways to best do so:
- Confidential Physician Feedback Reports: Designing for Optimal Impact on Performance is a guide that informs developers of feedback reports about evidence-based strategies to consider when they develop or refine a feedback reporting system.
- Will It Work Here? A Decisionmaker’s Guide to Adopting Innovations can help you determine if an innovation would be a good fit – or an appropriate stretch – for your practice or health care organization by asking a series of questions. It links users to actionable Web-based tools and presents case studies that illustrate how other organizations have addressed these questions.
- Improving Your Office Testing Process: A Toolkit for Rapid-Cycle Patient Safety and Quality Improvement provides information and resources to help physicians’ offices, clinics, and other ambulatory care facilities assess and improve the testing process in their offices.
These and other tools can be found at the AHRQ website.
Dr. Ganiats is the director for the National Center for Excellence in Primary Care Research at AHRQ.
This is the sixth in a series of articles from the National Center for Excellence in Primary Care Research in the Agency for Healthcare Research and Quality. This series introduces sets of tools and resources designed to help your practice.
Primary care practice is under increasing pressure to evolve. As highlighted in this series, topics such as shared decision making, team-based care, integration of behavioral health into primary care practice, and practice facilitation all offer the potential to enhance your primary care practice. On the other hand, quality of care must remain a top priority during this transformation. While much of the Agency for Healthcare Research and Quality’s (AHRQ) work in quality of care focuses on the inpatient setting, AHRQ offers many tools and resources to evaluate quality of care and to implement quality improvement into your primary care practice.
The NQMC mission is to provide an accessible mechanism for obtaining detailed information on quality measures and to further the dissemination, implementation, and use of these measures to inform health care decisions. NQMC is designed for practitioners, health care providers, health plans, integrated delivery systems, purchasers, and others interested in health care quality measurement. Funding for the NQMC is in question, and the future of this resource is not certain.
Confidential feedback reporting is widely considered to be a precursor to and a foundation for performance improvement. However, to enable change, the clinician responsible for and capable of change must receive, understand, and act on the information. The following publications from the National Center for Excellence in Primary Care Research offer some guidance from the on ways to best do so:
- Confidential Physician Feedback Reports: Designing for Optimal Impact on Performance is a guide that informs developers of feedback reports about evidence-based strategies to consider when they develop or refine a feedback reporting system.
- Will It Work Here? A Decisionmaker’s Guide to Adopting Innovations can help you determine if an innovation would be a good fit – or an appropriate stretch – for your practice or health care organization by asking a series of questions. It links users to actionable Web-based tools and presents case studies that illustrate how other organizations have addressed these questions.
- Improving Your Office Testing Process: A Toolkit for Rapid-Cycle Patient Safety and Quality Improvement provides information and resources to help physicians’ offices, clinics, and other ambulatory care facilities assess and improve the testing process in their offices.
These and other tools can be found at the AHRQ website.
Dr. Ganiats is the director for the National Center for Excellence in Primary Care Research at AHRQ.
AHA: Heart health helps optimize breast cancer outcomes
Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.
The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.
Cardiovascular disease and breast cancer are two entities that are frequently intertwined, Laxmi S. Mehta, MD, chair of the statement writing group, said in an interview.
“For any oncologic patient, it’s important to also consider their heart in the risk assessment because that also affects survival from the cancer,” said Dr. Mehta, the director of the Women’s Cardiovascular Health Program and an associate professor of medicine at the Ohio State University, Columbus.
Mortality risk attributable to CVD is higher in breast cancer survivors than in women who have no history of breast cancer, according to evidence Dr. Mehta and her colleagues cite in the statement.
Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.
Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.
Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.
A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.
Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.
Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.
To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.
In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.
Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.
Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.
“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.
Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.
SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.
Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.
The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.
Cardiovascular disease and breast cancer are two entities that are frequently intertwined, Laxmi S. Mehta, MD, chair of the statement writing group, said in an interview.
“For any oncologic patient, it’s important to also consider their heart in the risk assessment because that also affects survival from the cancer,” said Dr. Mehta, the director of the Women’s Cardiovascular Health Program and an associate professor of medicine at the Ohio State University, Columbus.
Mortality risk attributable to CVD is higher in breast cancer survivors than in women who have no history of breast cancer, according to evidence Dr. Mehta and her colleagues cite in the statement.
Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.
Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.
Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.
A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.
Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.
Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.
To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.
In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.
Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.
Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.
“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.
Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.
SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.
Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.
The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.
Cardiovascular disease and breast cancer are two entities that are frequently intertwined, Laxmi S. Mehta, MD, chair of the statement writing group, said in an interview.
“For any oncologic patient, it’s important to also consider their heart in the risk assessment because that also affects survival from the cancer,” said Dr. Mehta, the director of the Women’s Cardiovascular Health Program and an associate professor of medicine at the Ohio State University, Columbus.
Mortality risk attributable to CVD is higher in breast cancer survivors than in women who have no history of breast cancer, according to evidence Dr. Mehta and her colleagues cite in the statement.
Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.
Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.
Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.
A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.
Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.
Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.
To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.
In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.
Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.
Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.
“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.
Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.
SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.
FROM CIRCULATION
MS may be a transmissible protein misfolding disorder, study suggests
SAN DIEGO – MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.
Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”
This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.
The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.
Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.
In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.
Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.
In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.
At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.
While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.
The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.
Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.
The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.
The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.
SAN DIEGO – MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.
Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”
This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.
The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.
Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.
In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.
Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.
In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.
At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.
While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.
The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.
Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.
The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.
The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.
SAN DIEGO – MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.
Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”
This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.
The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.
Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.
In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.
Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.
In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.
At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.
While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.
The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.
Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.
The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.
The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Translational research suggests the primary damage in MS may be caused by transmissible protein misfolding.
Major finding: Transgenic mice over-expressing human prion protein that were injected with brain matter from MS patients developed various levels of significant pathology, and brain homogenate from these mice could transmit illness to naive transgenic mice.
Study details: Transgenic mice over-expressing human prion protein received intracerebral injection of brain homogenate from patients with primary or secondary-progressive MS
Disclosures: The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
Source: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.