Find all causes of Alzheimer's disease and a cure

Building on its enormously successful “Whole Genome Sequencing” Project, which identified nearly 1,000 new genetic mutations in more than 50 different genes, Cure Alzheimer's Fund has announced a new, even more ambitious multiyear, $50 million plus program titled “Genes to Therapies” (G2T). Simply put, the new project’s goal is to use the most promising recent genetic discoveries to develop drugs that would stop the disease at three separate stages: 

• For healthy people who don’t yet have Alzheimer’s: to stop Alzheimer’s before it starts by inhibiting the production of the Abeta protein and/or clearing it from the brain after it forms.

• For those exhibiting symptoms of Alzheimer’s: to stop the process early on by inhibiting the formation of tau tangles and protecting neurons from undue stress.

• For those whose disease has progressed significantly: to reduce the Abeta and tau-provoked inflammation, slowing down or even stopping the disease process.

“This is indeed a major challenge,” said Research Consortium Chair Dr. Rudy Tanzi, “but I believe we now have the data, the technology and the funding to take it on.” The first step, he explained, will be to prioritize approximately 15 genes that fit key several key criteria:

• They must have a clear impact on Alzheimer’s pathology.

• They must be “druggable”—connected to known biological systems, producing proteins similar to those already targeted by other drugs.

• They must impact one of the clear intervention points—Abeta/plaque production, tangle formation or neuroinflammation.

G2T will be aided significantly by the recent “Alzheimer’s-in-a-dish” breakthrough by Tanzi and Dr. Doo Kim at Massachusetts General Hospital. Using human brain cells generated from induced pluripotent stem (iPS) cells, Dr. Kim was—for the first time—able to create both the amyloid plaque and neurofibrillary tangle pathology of AD in a Petri dish. This technology will enable much cheaper and faster drug testing.

“Having learned much about the pathway that leads to disease, together with the genes responsible,” said Tanzi, “we now can proceed to look for chemical compounds that correct the defects. In other words, we can try to fix what is broken.”

Genes to Therapies (G2T) Steering Committee

To ensure the success of the G2T program, Cure Alzheimer’s Fund is funding a unique research facilitation process—the “infrastructure” for the project. This involves recruiting four researchers with expertise in specific genes and providing them with the specialty mice and reagents they will need to do their Alzheimer’s investigations relative to their particular genes. Unlike most projects, which require six to nine months’ preparation time before any real research begins, our unique approach will save money and, most importantly, time, allowing our researchers to get started right away.

Working as one, our G2T Steering Committee’s ultimate goal is to develop effective drug therapies at three different points in the pathological cascade of the disease to prevent, inhibit and cure Alzheimer’s. Here’s a quick look at each of the players.

Rudy Tanzi, Ph.D., chairman, Cure Alzheimer’s Fund Research Consortium

Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH)

Tanzi was the pioneering scientist who discovered the linkage between specific genes and Alzheimer’s disease. Today Tanzi leads the Alzheimer’s Genome Project™, a groundbreaking initiative dedicated to finding all the genes associated with Alzheimer’s disease so we can not only repair the damage the disease has caused, but prevent it from ever occurring. Tanzi’s role as chair of the G2T Steering Committee is to coordinate the efforts of the researchers as well as to continue his innovative research on what causes Alzheimer’s disease and how it develops.

Sam Sisodia, Ph.D., Cure Alzheimer’s Fund Research Consortium

Thomas A. Reynolds Sr. Family Professor of Neurosciences, University of Chicago

Director, Center for Molecular Neurobiology 

A longtime collaborator of Tanzi’s, Sisodia is a leading expert on the molecular and cell biology of Alzheimer’s disease pathology; he has been at the forefront of learning how the familial Alzheimer’s disease (FAD) genes, including the amyloid precursor protein and the presenilins, function normally and contribute to Alzheimer’s disease pathogenesis. His role on the committee is to help identify other researchers, beyond the Research Consortium, who are more familiar with designated genes. Sisodia was very instrumental in designing and implementing the unique “infrastructure” to facilitate more rapid and cost-effective research program for Genes to Therapies.

Dave Michael Holtzman, M.D., Cure Alzheimer’s Fund Research Consortium

The Andrew B. and Gretchen P. Jones Professor of Neurology and Head of the Department of Neurology, Washington University, St. Louis

Like Sisodia, Dr. Holtzman has a background in biology and has helped to identify the most effective interventions from specific gene functional variants in Alzheimer’s disease. Dr. Holtzman is involved in clinical and research activities at the Washington University Memory and Aging Project and the Alzheimer’s Disease Research Center. He has contributed greatly to our understanding of how anti-amyloid antibodies affect Alzheimer’s pathology and how Abeta is cleared from the brains of Alzheimer’s patients. As a member of the steering committee, he will assist in identifying other researchers with similar skills to investigate how the designated Alzheimer’s genes affect the pathology, and bring his clinical experience to bear in setting priorities for potential drug development.

Steven Wagner, Ph.D., Cure Alzheimer’s Fund Research Consortium
Principal Investigator, Department of Neurosciences, School of Medicine, University of California, San Diego

Wagner has an extensive background in biochemistry and drug discovery and has numerous patents to his name. Along with Tanzi, he helped develop the first gamma-secretase inhibitor for Alzheimer’s disease, which later provided the platform for gamma-secretase modulators, which control amyloid production rather than stop it altogether. “If we administer this at the right time to the right populations, it could help to slow down the disease process,” said Wagner. As a member of the steering committee, he will focus on genes that may provide clues for early prevention.

Robert Vassar, Ph.D., Cure Alzheimer’s Fund Research Consortium

Professor of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University

Vassar’s ongoing research focuses on the role of Abeta and the enzyme BACE1 in normal biological processes and in disease mechanisms of relevance to Alzheimer’s disease. As a pioneer in Alzheimer’s research, Bob has made a number of discoveries critical to progress in the field. As a member of the Genes to Therapies Steering Committee, he will help ensure proper attention is paid in the G2T research projects to the more basic aspects of how Alzheimer’s-relevant genes are produced and how they affect the disease pathology.

Wilma Wasco, Ph.D.

Associate Professor of Neurology, Genetics and Aging Research Unit,

Massachusetts General Institute for Neurodegenerative Disease, Harvard Medical School and Massachusetts General Hospital 

Wasco was part of an international collaborative effort that identified the familial Alzheimer’s disease-associated presenilin 1 (PS1) and presenilin 2 (PS2) genes. Her research has evolved to focus on understanding the biological role certain AD-linked proteins play in the normal, aging and diseased brain. As research operations manager for the G2T project, Wasco will be responsible for facilitating communication among the various researchers, and managing and maintaining the core facilities and research materials, including specially engineered laboratory mice. She also will develop and maintain a G2T publications resource and provide the operations management necessary for this complex and unique undertaking.

Tim Armour, president and CEO, Cure Alzheimer’s Fund
Armour brings an extensive background in nonprofits and fundraising to Cure Alzheimer’s Fund as well as an MBA. from Harvard. Armour joined Cure Alzheimer’s Fund 10 years ago to help lead the charge in the quest for a cure. As the administrator of the steering committee, Armour is responsible for supporting the researchers, developing and securing budgets, and being the liaison between the committee and the Cure Alzheimer’s Fund Board of Directors.