CART Grants

Alzheimer’s disease is sometimes called “the diabetes” of the brain, because, like diabetes, it is common and shares some common features including accumulation of proteinaceous deposits called amyloid. Moreover, until recently, it wasn’t apparent that diabetes itself is a risk factor for AD, and insulin, a key hormone regulating the body’s ability to respond to glucose (“sugar”) levels in the blood and centrally involved in the pathogenesis of diabetes, also has important effects on brain cells and the cellular and molecular processes involved in AD. Dr. Murphy’s exciting research proposal will study the shared mechanisms involved in AD and diabetes, and another new link between them – obesity.

Accumulation of a toxic protein fragment known as the amyloid beta peptide (Aß) in the brain is belieed to play an important role in Alzheimer’s disease., and as such, there is worldwide interest in developing new ways to reduce the build up Aß in the brain as a therapeutic strategy for prevention and treatment of AD. Dr. Puglieili’s CART research grant takes an entirely novel and promising approach to reducing amyloid production in the brain. His research will capitalize on promising preliminary finding s and discovery of new drug-like compounds that appear to change the activity of another key protein, called BACE1 (the Beta Amyloid Converting Enzyme). Further development of these and other related compounds in this research could lead to new drugs that reduce Aß production in a more safe way than other strategies under development.

Statement from Dr. Puglielli
Most of the newly-discovered drugs are ultimately abandoned (because unsuccessful), it is often difficult to attract funding for the research. The CART grant provided us with the necessary funding in a moment of high need and has been crucial for the early stages of our studies. The road to the discovery of a cure for Alzheimer’s disease is a long one but if we succeed we will always be thankful to the CART grant.

Dr. Burnden’s proposal is close behind Puglieli’s in terms of proximity to animal model testing, after Brunden does some toxicology. Brudens proposal focuses on a family of aminothienopyridizine (ATPZs) compounds that emerged from 290,000 compound screens for drugs to block tangle formation in AD. He has identified several ATPZs that are worthy of bringing forward in animal studies.

Dr. Hyman directs the Alzheimer’s disease research unit at the MassGeneral Institute for Neurodegenerative Disease (www.mghmind.org), with the goal of understanding the neuropathophysiologic and genetic factors that underlie dementia. His laboratory studies the anatomical and molecular basis of dementia in Alzheimer’s disease and dementia with Lewy bodies.

Dr. Hyman received his M.D. and Ph.D. from the University of Iowa and he has received the Metropolitan Life Award, the Potamkin Prize, a National Institute on Aging MERIT award, and an Alzheimer Association Pioneer Award. He has been the Director of the Massachusetts Alzheimer’s Disease Research Center since 2006.

Dr. Landreth is a professor in the Department of Neurosciences at Case Western Reserve University. He received his undergraduate degree in Chemistry and Biochemistry from the University of Kansas in 1972. He then completed a Ph.D. in the Neurosciences Program at the University of Michigan, including a year of study at the National Institute of Medical Research in London. He did postdoctoral work in the Department of Neurobiology at Stanford. His work has focused on investigation of the biological basis of Alzheimer’s disease and development of new therapies for its treatment.

Dr. Burnden’s proposal is close behind Puglieli’s in terms of proximity to animal model testing, after Brunden does some toxicology. Brudens proposal focuses on a family of aminothienopyridizine (ATPZs) compounds that emerged from 290,000 compound screens for drugs to block tangle formation in AD. He has identified several ATPZs that are worthy of bringing forward in animal studies.