AD Prevention Initiative Could Lead to Large Trials

SANTA FE, N.M. – A privately funded initiative is gearing up to do proof-of-concept prevention trials sooner rather than later in motivated volunteers who carry susceptibility genes for early Alzheimer's disease, but have not yet presented with cognitive impairment.

If any treatments can be shown to prevent precursor brain imaging and biomarker changes, the investigators plan to launch large clinical trials in people who have put their names into an Arizona Alzheimer's Consortium registry of potential participants.

Dr. Pierre N. Tariot announced the initiative at an annual psychiatric symposium sponsored by the University of Arizona. An advisory group of leading investigators will meet in Phoenix in October to set priorities in preparation for requesting a grant from the National Institutes of Health, he told attendees.

“The Holy Grail is either to delay the onset of the illness or prevent it altogether,” said Dr. Tariot, director of the Memory Disorders Center at Banner Alzheimer's Institute in Phoenix. “If we can delay the onset by 5 years we could cut the numbers in half. That is a huge impact. We think that is an achievable goal.”

The general schema, as outlined by Dr. Tariot, is to genotype asymptomatic people who are in their early 40s and come from families with a history of early Alzheimer's disease. Those who screen positive for genes that predict they will develop dementia within the next decade could be invited to participate in one of a series of small placebo-controlled studies.

Within 2 years, the investigators expect to see whether an intervention can alter the course of changes leading to the disease. Rather than waiting years more to see whether the disease is prevented in these subjects, the project would start a clinical trial of a promising therapy in a larger population drawn from the registry at this point.

“The development work has already been done showing what happens to your brain with various types of imaging and biomarkers before you get the illness. … If I have an anti-amyloid therapy I am going to test it in 100 people–50 on drug and 50 on placebo. That is enough to answer the question of whether the trajectory is altered or not,” Dr. Tariot said.

Estrogen, antioxidants, omega-3 fatty acids, exercise, memantine, and other “emerging experimental therapies” also are among the potential interventions under consideration for proof-of-concept studies. Therapies that failed in Alzheimer's intervention trials would not be ruled out, but they must be proven safe, Dr. Tariot said. Hormonal therapies, in particular, might be effective in preventing the disease, even if they cannot stop its progression.

“We think that right now there are roughly a dozen Alzheimer's prevention interventions that might work,” he said.

Except for the publicly funded registry, the investigators are relying on private philanthropy to jump-start the initiative. Dr. Tariot was optimistic that the NIH will be receptive as the project matures, but noted that, despite unanimous enthusiasm for the concept, industry and government have been cautious thus far.

“It is so out of the box, we are not getting any funding,” he said. “So we are actually using philanthropic dollars to launch this initiative. We think once we get going, the field will be changed forever.”

Building an infrastructure for clinical trials is a priority for Dr. Tariot and his colleagues. Along with the research registry, this entails writing protocols for an administrative structure and a scientific and ethical review process, including data and safety monitoring boards that could be in place when the larger trials are funded and ready to start.

The Arizona Alzheimer's Consortium hosts the registry at its Web site, www.azalz.org

Based on their responses to a detailed questionnaire and their location in the state, volunteers are referred to research studies at one or more of the consortium's eight member institutions: Arizona State University, Banner Alzheimer's Institute, Barrow Neurological Institute, Mayo Clinic Arizona, Sun Health Research Institute, Translational Genomics Research Institute, Tucson VA, and the University of Arizona.

Efforts are underway to expand the registry, and thereby the pool of potential volunteers, to other Western states.“There are so many therapies in development that the biggest threat to finding a way to put Alzheimer's disease behind us is not discovery any more. It is clinical trials,” Dr. Tariot said.

He disclosed relationships, including consulting fees and research support, with about 24 companies engaged in Alzheimer's research, but emphasized that he has no investments to disclose and does not serve on any speakers bureaus. Banner Alzheimer's Institute is part of the nonprofit Banner Health System, and has the Banner Alzheimer's Foundation as a philanthropic resource.

SANTA FE, N.M. – A privately funded initiative is gearing up to do proof-of-concept prevention trials sooner rather than later in motivated volunteers who carry susceptibility genes for early Alzheimer's disease, but have not yet presented with cognitive impairment.

If any treatments can be shown to prevent precursor brain imaging and biomarker changes, the investigators plan to launch large clinical trials in people who have put their names into an Arizona Alzheimer's Consortium registry of potential participants.

Dr. Pierre N. Tariot announced the initiative at an annual psychiatric symposium sponsored by the University of Arizona. An advisory group of leading investigators will meet in Phoenix in October to set priorities in preparation for requesting a grant from the National Institutes of Health, he told attendees.

“The Holy Grail is either to delay the onset of the illness or prevent it altogether,” said Dr. Tariot, director of the Memory Disorders Center at Banner Alzheimer's Institute in Phoenix. “If we can delay the onset by 5 years we could cut the numbers in half. That is a huge impact. We think that is an achievable goal.”

The general schema, as outlined by Dr. Tariot, is to genotype asymptomatic people who are in their early 40s and come from families with a history of early Alzheimer's disease. Those who screen positive for genes that predict they will develop dementia within the next decade could be invited to participate in one of a series of small placebo-controlled studies.

Within 2 years, the investigators expect to see whether an intervention can alter the course of changes leading to the disease. Rather than waiting years more to see whether the disease is prevented in these subjects, the project would start a clinical trial of a promising therapy in a larger population drawn from the registry at this point.

“The development work has already been done showing what happens to your brain with various types of imaging and biomarkers before you get the illness. … If I have an anti-amyloid therapy I am going to test it in 100 people–50 on drug and 50 on placebo. That is enough to answer the question of whether the trajectory is altered or not,” Dr. Tariot said.

Estrogen, antioxidants, omega-3 fatty acids, exercise, memantine, and other “emerging experimental therapies” also are among the potential interventions under consideration for proof-of-concept studies. Therapies that failed in Alzheimer's intervention trials would not be ruled out, but they must be proven safe, Dr. Tariot said. Hormonal therapies, in particular, might be effective in preventing the disease, even if they cannot stop its progression.

“We think that right now there are roughly a dozen Alzheimer's prevention interventions that might work,” he said.

Except for the publicly funded registry, the investigators are relying on private philanthropy to jump-start the initiative. Dr. Tariot was optimistic that the NIH will be receptive as the project matures, but noted that, despite unanimous enthusiasm for the concept, industry and government have been cautious thus far.

“It is so out of the box, we are not getting any funding,” he said. “So we are actually using philanthropic dollars to launch this initiative. We think once we get going, the field will be changed forever.”

Building an infrastructure for clinical trials is a priority for Dr. Tariot and his colleagues. Along with the research registry, this entails writing protocols for an administrative structure and a scientific and ethical review process, including data and safety monitoring boards that could be in place when the larger trials are funded and ready to start.

The Arizona Alzheimer's Consortium hosts the registry at its Web site, www.azalz.org

Based on their responses to a detailed questionnaire and their location in the state, volunteers are referred to research studies at one or more of the consortium's eight member institutions: Arizona State University, Banner Alzheimer's Institute, Barrow Neurological Institute, Mayo Clinic Arizona, Sun Health Research Institute, Translational Genomics Research Institute, Tucson VA, and the University of Arizona.

Efforts are underway to expand the registry, and thereby the pool of potential volunteers, to other Western states.“There are so many therapies in development that the biggest threat to finding a way to put Alzheimer's disease behind us is not discovery any more. It is clinical trials,” Dr. Tariot said.

He disclosed relationships, including consulting fees and research support, with about 24 companies engaged in Alzheimer's research, but emphasized that he has no investments to disclose and does not serve on any speakers bureaus. Banner Alzheimer's Institute is part of the nonprofit Banner Health System, and has the Banner Alzheimer's Foundation as a philanthropic resource.

SANTA FE, N.M. – A privately funded initiative is gearing up to do proof-of-concept prevention trials sooner rather than later in motivated volunteers who carry susceptibility genes for early Alzheimer's disease, but have not yet presented with cognitive impairment.

If any treatments can be shown to prevent precursor brain imaging and biomarker changes, the investigators plan to launch large clinical trials in people who have put their names into an Arizona Alzheimer's Consortium registry of potential participants.

Dr. Pierre N. Tariot announced the initiative at an annual psychiatric symposium sponsored by the University of Arizona. An advisory group of leading investigators will meet in Phoenix in October to set priorities in preparation for requesting a grant from the National Institutes of Health, he told attendees.

“The Holy Grail is either to delay the onset of the illness or prevent it altogether,” said Dr. Tariot, director of the Memory Disorders Center at Banner Alzheimer's Institute in Phoenix. “If we can delay the onset by 5 years we could cut the numbers in half. That is a huge impact. We think that is an achievable goal.”

The general schema, as outlined by Dr. Tariot, is to genotype asymptomatic people who are in their early 40s and come from families with a history of early Alzheimer's disease. Those who screen positive for genes that predict they will develop dementia within the next decade could be invited to participate in one of a series of small placebo-controlled studies.

Within 2 years, the investigators expect to see whether an intervention can alter the course of changes leading to the disease. Rather than waiting years more to see whether the disease is prevented in these subjects, the project would start a clinical trial of a promising therapy in a larger population drawn from the registry at this point.

“The development work has already been done showing what happens to your brain with various types of imaging and biomarkers before you get the illness. … If I have an anti-amyloid therapy I am going to test it in 100 people–50 on drug and 50 on placebo. That is enough to answer the question of whether the trajectory is altered or not,” Dr. Tariot said.

Estrogen, antioxidants, omega-3 fatty acids, exercise, memantine, and other “emerging experimental therapies” also are among the potential interventions under consideration for proof-of-concept studies. Therapies that failed in Alzheimer's intervention trials would not be ruled out, but they must be proven safe, Dr. Tariot said. Hormonal therapies, in particular, might be effective in preventing the disease, even if they cannot stop its progression.

“We think that right now there are roughly a dozen Alzheimer's prevention interventions that might work,” he said.

Except for the publicly funded registry, the investigators are relying on private philanthropy to jump-start the initiative. Dr. Tariot was optimistic that the NIH will be receptive as the project matures, but noted that, despite unanimous enthusiasm for the concept, industry and government have been cautious thus far.

“It is so out of the box, we are not getting any funding,” he said. “So we are actually using philanthropic dollars to launch this initiative. We think once we get going, the field will be changed forever.”

Building an infrastructure for clinical trials is a priority for Dr. Tariot and his colleagues. Along with the research registry, this entails writing protocols for an administrative structure and a scientific and ethical review process, including data and safety monitoring boards that could be in place when the larger trials are funded and ready to start.

The Arizona Alzheimer's Consortium hosts the registry at its Web site, www.azalz.org

Based on their responses to a detailed questionnaire and their location in the state, volunteers are referred to research studies at one or more of the consortium's eight member institutions: Arizona State University, Banner Alzheimer's Institute, Barrow Neurological Institute, Mayo Clinic Arizona, Sun Health Research Institute, Translational Genomics Research Institute, Tucson VA, and the University of Arizona.

Efforts are underway to expand the registry, and thereby the pool of potential volunteers, to other Western states.“There are so many therapies in development that the biggest threat to finding a way to put Alzheimer's disease behind us is not discovery any more. It is clinical trials,” Dr. Tariot said.

He disclosed relationships, including consulting fees and research support, with about 24 companies engaged in Alzheimer's research, but emphasized that he has no investments to disclose and does not serve on any speakers bureaus. Banner Alzheimer's Institute is part of the nonprofit Banner Health System, and has the Banner Alzheimer's Foundation as a philanthropic resource.