Innervation Is Maintained for 24 Years After Transplantation in Parkinson’s Disease

Transplanted nerve cells may survive for nearly a quarter of a century in a patient’s brain despite ongoing Parkinson’s disease, according to data published online ahead of print May 2 in the Proceedings of the National Academy of Sciences of the United States of America. A transplant of cells into the putamen yields dense reinnervation similar to that of healthy brains. The case study also suggests that the initial clinical benefits of the transplant gradually deteriorate when pathology spreads from the patient’s brain to the transplanted cells.

“This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain,” said Olle Lindvall, MD, PhD, Professor of Clinical Neurology and Chairman of Neurology at the University Hospital in Lund, Sweden. “At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”

Olle Lindvall, MD, PhD

Dr. Lindvall and colleagues followed a patient with Parkinson’s disease for 24 years after he received a transplant of embryonic dopaminergic neurons. The patient had developed Parkinson’s disease in 1980 and had started L-dopa treatment in 1982. The therapy appeared to be efficacious, but in 1986, the patient developed “on–off” symptoms. During “off” periods, he experienced resting tremor, hypokinetic movements, and rigidity, especially on the left side of his body. During “on” periods, he displayed mild parkinsonian symptoms.

In 1989, the patient, who was then age 59, underwent transplantation with ventral mesencephalic tissue from four human embryos into the right putamen. He was monitored for 10 years post transplantation. In the first three years, researchers noted significant improvement, and L-dopa was withdrawn at 32 months. At 64 months post transplantation, immunosuppressive treatment was stopped. When symptoms progressed at 74 months, a low dose of L-dopa was reintroduced. The patient had a marked clinical benefit, including a near-absence of rigidity, at 10 years. At 12 years, however, he had worsening hypokinesia; as a result, a low-dose dopamine agonist was added for two years, and the L-dopa dose was increased.

The patient responded well to his treatment change at first, but at 14 years, his condition worsened. He began to experience increasing rigidity, hypokinesia, and a gradual loss of beneficial L-dopa response. During this time, cognitive impairment and onset of progressive dementia were first noted. At 18 years, no graft-related motor improvement remained, and the patient was unable to walk, swallow, or speak. At 24 years, the patient died of cardiac insufficiency. Autopsy revealed no evidence of an ongoing immune or inflammatory response. The patient had a dense, near-normal dopaminergic reinnervation derived from the grafts at 24 years post transplantation.

This case study provides the first evidence that rich dopaminergic innervation that develops in the first three years after transplantation and causes dramatic motor improvement can be preserved for 24 years in Parkinson’s disease, according to the authors. The clinical results, however, showed that even a viable graft could eventually lose its efficacy if widespread alpha-synucleinopathy progresses and degeneration occurs in the host brain.

“This study is completely unique,” said Anders Bjorklund, Professor at the Wallenberg Neuroscience Center at Lund University. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period...What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”

—Erica Robinson

Transplanted nerve cells may survive for nearly a quarter of a century in a patient’s brain despite ongoing Parkinson’s disease, according to data published online ahead of print May 2 in the Proceedings of the National Academy of Sciences of the United States of America. A transplant of cells into the putamen yields dense reinnervation similar to that of healthy brains. The case study also suggests that the initial clinical benefits of the transplant gradually deteriorate when pathology spreads from the patient’s brain to the transplanted cells.

“This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain,” said Olle Lindvall, MD, PhD, Professor of Clinical Neurology and Chairman of Neurology at the University Hospital in Lund, Sweden. “At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”

Olle Lindvall, MD, PhD

Dr. Lindvall and colleagues followed a patient with Parkinson’s disease for 24 years after he received a transplant of embryonic dopaminergic neurons. The patient had developed Parkinson’s disease in 1980 and had started L-dopa treatment in 1982. The therapy appeared to be efficacious, but in 1986, the patient developed “on–off” symptoms. During “off” periods, he experienced resting tremor, hypokinetic movements, and rigidity, especially on the left side of his body. During “on” periods, he displayed mild parkinsonian symptoms.

In 1989, the patient, who was then age 59, underwent transplantation with ventral mesencephalic tissue from four human embryos into the right putamen. He was monitored for 10 years post transplantation. In the first three years, researchers noted significant improvement, and L-dopa was withdrawn at 32 months. At 64 months post transplantation, immunosuppressive treatment was stopped. When symptoms progressed at 74 months, a low dose of L-dopa was reintroduced. The patient had a marked clinical benefit, including a near-absence of rigidity, at 10 years. At 12 years, however, he had worsening hypokinesia; as a result, a low-dose dopamine agonist was added for two years, and the L-dopa dose was increased.

The patient responded well to his treatment change at first, but at 14 years, his condition worsened. He began to experience increasing rigidity, hypokinesia, and a gradual loss of beneficial L-dopa response. During this time, cognitive impairment and onset of progressive dementia were first noted. At 18 years, no graft-related motor improvement remained, and the patient was unable to walk, swallow, or speak. At 24 years, the patient died of cardiac insufficiency. Autopsy revealed no evidence of an ongoing immune or inflammatory response. The patient had a dense, near-normal dopaminergic reinnervation derived from the grafts at 24 years post transplantation.

This case study provides the first evidence that rich dopaminergic innervation that develops in the first three years after transplantation and causes dramatic motor improvement can be preserved for 24 years in Parkinson’s disease, according to the authors. The clinical results, however, showed that even a viable graft could eventually lose its efficacy if widespread alpha-synucleinopathy progresses and degeneration occurs in the host brain.

“This study is completely unique,” said Anders Bjorklund, Professor at the Wallenberg Neuroscience Center at Lund University. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period...What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”

—Erica Robinson

Transplanted nerve cells may survive for nearly a quarter of a century in a patient’s brain despite ongoing Parkinson’s disease, according to data published online ahead of print May 2 in the Proceedings of the National Academy of Sciences of the United States of America. A transplant of cells into the putamen yields dense reinnervation similar to that of healthy brains. The case study also suggests that the initial clinical benefits of the transplant gradually deteriorate when pathology spreads from the patient’s brain to the transplanted cells.

“This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain,” said Olle Lindvall, MD, PhD, Professor of Clinical Neurology and Chairman of Neurology at the University Hospital in Lund, Sweden. “At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”

Olle Lindvall, MD, PhD

Dr. Lindvall and colleagues followed a patient with Parkinson’s disease for 24 years after he received a transplant of embryonic dopaminergic neurons. The patient had developed Parkinson’s disease in 1980 and had started L-dopa treatment in 1982. The therapy appeared to be efficacious, but in 1986, the patient developed “on–off” symptoms. During “off” periods, he experienced resting tremor, hypokinetic movements, and rigidity, especially on the left side of his body. During “on” periods, he displayed mild parkinsonian symptoms.

In 1989, the patient, who was then age 59, underwent transplantation with ventral mesencephalic tissue from four human embryos into the right putamen. He was monitored for 10 years post transplantation. In the first three years, researchers noted significant improvement, and L-dopa was withdrawn at 32 months. At 64 months post transplantation, immunosuppressive treatment was stopped. When symptoms progressed at 74 months, a low dose of L-dopa was reintroduced. The patient had a marked clinical benefit, including a near-absence of rigidity, at 10 years. At 12 years, however, he had worsening hypokinesia; as a result, a low-dose dopamine agonist was added for two years, and the L-dopa dose was increased.

The patient responded well to his treatment change at first, but at 14 years, his condition worsened. He began to experience increasing rigidity, hypokinesia, and a gradual loss of beneficial L-dopa response. During this time, cognitive impairment and onset of progressive dementia were first noted. At 18 years, no graft-related motor improvement remained, and the patient was unable to walk, swallow, or speak. At 24 years, the patient died of cardiac insufficiency. Autopsy revealed no evidence of an ongoing immune or inflammatory response. The patient had a dense, near-normal dopaminergic reinnervation derived from the grafts at 24 years post transplantation.

This case study provides the first evidence that rich dopaminergic innervation that develops in the first three years after transplantation and causes dramatic motor improvement can be preserved for 24 years in Parkinson’s disease, according to the authors. The clinical results, however, showed that even a viable graft could eventually lose its efficacy if widespread alpha-synucleinopathy progresses and degeneration occurs in the host brain.

“This study is completely unique,” said Anders Bjorklund, Professor at the Wallenberg Neuroscience Center at Lund University. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period...What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”

—Erica Robinson