Faculty Mount an Aging Brain Effort

Faculty Mount an Aging Brain Effort to Tackle Neuro-Degenerative Disease. 

“Where is the war on Alzheimer’s disease?” asks Michael Sipser, Dean of Science, and he is not alone. There is clearly a tremendous need – and great urgency – to address the burdens of the aging brain and the co-morbidities it spawns, from cognitive decline to Alzheimer’s disease (AD) and other dementias of aging. 
 
This is a global health challenge. Dementias of aging now claim 35 million victims worldwide, and the numbers will double every 20 years as life expectancy rises and the population ages. In our lifetimes, one in three of us will fall victim to AD or a dementia of aging. The annual cost of dementias worldwide – now estimated at $604 billion – is growing faster than the number of sufferers. 
 
And while other causes of death have declined in the past decade, AD has risen an alarming 46%. 5.2 million Americans now have AD, and by 2050 the number will rise to 13.8 million. AD-related Medicare and Medicaid expenses were $150 billion in 2014, making it our greatest healthcare cost – greater than cancer or heart disease. 
 
Without breakthrough treatments, in 30 years AD threatens not only to bankrupt Medicare, but also to impoverish healthcare systems worldwide. Of the annual worldwide cost of AD care, 70% is spent on informal social and direct medical care. These social and economic challenges will only intensify as life expectancy rises across the globe.
 
The Knowledge Gap 
Great strides have been made in diagnosing and treating other morbidities of aging, like diabetes, cancer, and heart disease. However, those strides have yet to come in AD and dementias because we know so little about their basic biology and what causes brain functions to change with age. No patient diagnosed with AD has ever recovered, and no effective disease-modifying therapies have been developed. 
 
Dementia is not a normal or inevitable part of the aging process. We do know that the brain is the control center of the systemic aging process and is highly vulnerable to damage over time. We also know that some of us are protected from these degenerative processes while others are not. 
 
Lead Investigator Li-Huei Tsai, Picower Professor of Neuroscience and Director of the Picower Institute for Learning and Memory, insists that “in order to conquer AD and dementias, we need to understand both what causes these degenerative processes and also why some of us are protected from them. We need to understand the genetic, biochemical, cellular, circuit, behavioral, and environmental factors behind cognitive decline and how these components function, interact, and overlap to regulate aging and neurodegeneration. Finally, we need to know which pathways and biological targets are amenable to diagnostic, prognostic, or therapeutic intervention.”
 
Lack of Sufficient Funding and No Cure
These are formidable challenges. Making them more difficult is the fact that government funding for dementia research lags far behind other diseases: this year, we will spend $5.4 billion on cancer research, $3 billion on HIV/AIDS research, and $1.2 billion on heart disease research, but just $566 million on AD.
 
Meanwhile, in the past two years the FDA has approved 19 new cancer drugs, with more in the pipeline. In contrast, not a single new AD drug has been approved in the past decade. The reason is simple: More than 40 years of investment in basic cancer research has made the disease much better understood than AD, and this understanding has led to successful translational research. Today’s oncology drugs could not have been developed without this foundational knowledge. But this fundamental information is largely missing in AD, so it’s not surprising that inadequate research investment has yielded no effective treatment. The clinical landscape is littered with more than a hundred failed attempts to develop effective treatments; the success rate among independent trials is just 5%.
 
The Need for Basic Research 
The disappointing performance of almost every drug in Phase III clinical trials points to an urgent need to increase both the amount of basic research taking place and the speed with which we conduct it. It has become clear that there are likely many causes of AD and many different genetic mutations that increase the risk for the disease, yet almost all the clinical trials of potential AD drugs have focused on just a single biological pathway that leads to amyloid deposition while other causes remain largely unexplored.
 
Basic research in brain aging is one of the most cost-effective approaches to fighting age-related disease. Recent calculations by Andrew Lo, Charles E. and Susan T. Harris Professor of Finance at MIT, suggest that a new therapy resulting from this research – a therapy which delays the onset of AD by 5 years – could save Medicare/Medicaid $200 billion over the next decade and $1.5 trillion over the next 30 years. 
 
According to Susan Lindquist, Professor of Biology and member of the Whitehead Institute, “The Aging Brain Effort is a proposal to begin this process of foundational research and its rapid integration into the clinical setting, and to establish an investment platform for long-term commitments to address this global health imperative.”
 
The Aging Brain Effort at MIT would be the first collaborative effort focused exclusively on researching the aging brain. Though there are academic departments of neuroscience which are invested in AD research, aging institutes dedicated to general lifespan issues(including the Buck Institute for Research on Aging, Glenn Centers for Aging Research, and the National Institute on Aging), and even comprehensive clinical care facilities like Harvard Medical School’s Aging Brain Center and Albert Einstein College’s translational program for clinical care of dementia – there is currently no center devoted to fundamental research on the aging brain.
 
We hope to bring together today’s leading researchers in health, aging, and Alzheimer’s disease in an integrated, multidisciplinary, highly collaborative group that includes the neurosciences, biology, engineering, computer science, artificial intelligence, and the clinical environment, as well as healthcare economics, manufacturing, and technology transfer. The result would be the first multidisciplinary, multi-institutional basic research group for the study of the neurological mechanisms that underlie brain aging. Its focus would be on aging brain research not previously attempted, and its mission would be to integrate core sciences and technologies across a wide range of fields and apply them to the field of aging, building from multiple domains to create a comprehensive understanding of the aging brain in health and cognitive decline. 
 
Building on MIT’s Strengths 
The founders of the initiative include renowned MIT researchers Li-Huei Tsai, Edward Boyden ’99 (VI-2, VIII), MNG ’99 (VI P), Emery N. Brown, Leonard Guarente, H. Robert Horvitz, and Susan Lindquist. They are joined by distinguished collaborators at MIT, the Whitehead Institute, the Broad Institute, Massachusetts General Hospital, Harvard Medical School, the greater Boston medical research community, and other leaders in the national and global scientific community. The Aging Brain Effort would be ideally positioned to leverage MIT’s exceptional laboratory and educational infrastructure, its leadership in hard sciences and engineering, its intellectual capital and entrepreneurial culture, and its proximity to the Kendall Square commercialization corridor, which acts as a unique vehicle for pharmaceutical development and technology transfer.
 
We Need Your Help
We have the talent and the tools and we know what must be done to win the war against Alzheimer’s disease and the dementias of aging. The Aging Brain Effort at MIT would focus a unique range of scientific talent on a single goal: improving our future through a thorough understanding of the aging brain. Our greatest challenge is to fund this future. We must find the resources to execute groundbreaking basic research despite the paucity of government funding. Private philanthropy can make a significant difference in this critical problem of our lifetimes. Please consider a gift in support of this effort. If you would like to receive further information about this project, please contact Elizabeth Chadis, Assistant Dean, at 617.253.8903 or echadis@mit.edu.
 
About Our Founding Investigators
Edward Boyden, Ph.D. Associate Professor of Biological Engineering and Brain and Cognitive Sciences, MIT Media Lab and the McGovern Institute for Brain Research. Boyden ’99 (VI-2, VIII), MNG ’99 (VI P) engineers tools for mapping, controlling, observing, and building dynamic circuits of the brain. He has developed “optogenetic” tools to activate and silence neurons with light. In 2010 his approach was recognized as the “Method of the Year” by Nature Methods and is now in worldwide use. 
 
Emery N. Brown, M.D., Ph.D. Edward Hood Taplin Professor of Medical Engineering, Institute for Medical Engineering and Science and Professor of Computational Neuroscience, Department of Brain and Cognitive Sciences, MIT and Massachusetts General Hospital. An anesthesiologist-statistician, Brown has developed signal processing algorithms that characterize how the brain represents and transmits information. He has made important contributions to understanding how anesthetics act in the brain and how their impact changes with age.
 
Leonard Guarente, Ph.D. Novartis Professor of Biology, MIT. Guarente is an expert in the longevity of species from yeast to mammals and has identified potent anti-aging regimens. He found sirtuin proteins central to diet and stress adaptation and to combating diseases of aging, like cancer and neurodegenerative disease.
 
H. Robert Horvitz, Ph.D. David H. Koch Professor of Biology, MIT. Horvitz uses the genetics of the nematode worm (C. Elegans) to understand neuro-development, behavior, and neurodegenerative disease. He received the 2002 Nobel Prize in Physiology or Medicine for his discoveries concerning the genetic regulation of organ development and programmed cell death.
 
Susan Lindquist, Ph.D. Professor, Department of Biology, MIT and the Whitehead Institute. Lindquist has pioneered studies of protein homeostasis and protein folding, particularly as it pertains to heat-shock proteins and prions. She has discovered processes in the rapid evolution of new traits, cancer, neurodegenerative disease, and microbial drug resistance. She was awarded the President’s National Medal of Science in 2010.
 
Li-Huei Tsai, Ph.D. Lead Investigator, Aging Brain Effort. Director, The Picower Institute for Learning and Memory and Picower Professor of Neuroscience, Department of Brain and Cognitive Sciences, MIT. Tsai combines molecular, genetic, and circuit approaches to understanding the pathophysiology of neurological disorders affecting cognition as we age. Her discoveries in Alzheimer’s-like disease research, including therapeutic reversal strategies for cognitive defects, have been highlighted in Nature, Cell, and Neuron

 

SUPPORT THE SCHOOL OF SCIENCE
Please contact Elizabeth Chadis if you are considering a gift to the School of Science:

Elizabeth Chadis

Assistant Dean for Development
t: 6172538903
e: ECHADIS@MIT.EDU