Cure Alzheimer’s Fund, a Massachusetts-based nonprofit dedicated to funding promising research into ways to prevent, slow, or reverse Alzheimer’s disease, has awarded more than $700,000 in research grants in September to scientists working toward those goals.
The five newly funded projects brings Cure Alzheimer’s research support for 2016 to more than $6 million, given to some 29 scientific efforts.
“Every day, researchers continue to make important contributions in our understanding of Alzheimer’s disease and in finding ways to treat it,” Tim Armour, Cure Alzheimer’s president and CEO, said in a press release. “We are honored to help these researchers at the earliest stages of their work, as they develop their projects and our comprehension of this intricate disease.”
The five projects are:
Binding Site Characterization of a Novel Pyridazine-Derived Class of y-Secretase Modulators ($194,950)
The purpose of this study, by Steven Wagner, PhD, principal investigator in the Department of Neurosciences at the University of California, San Diego, School of Medicine, is to identify critical sites of interaction between pyridazine-derives soluble gamma secretase modulators (SGSMs) and their molecular target. Researchers also aim to better understand the mechanism by which these therapeutically relevant small molecules affect specific amyloid beta (Abeta) peptide variant production without inhibiting the enzyme’s activity. Currently, the precise molecular target and mechanism of action of this pyridazine series remain unknown.
Uncovering Determinants of Neuronal Vulnerability in Alzheimer’s Disease, Year 2 ($250,000)
This project, by Paul Greengard, PhD, Vincent Astor Professor in the Laboratory of Molecular and Cellular Neuroscience at Rockefeller University in New York, will test three gene mutations to determine whether they are potential causes of Alzheimer’s. The Greengard laboratory studies molecular defects responsible for neurological and psychiatric disorders, including Alzheimer’s, Parkinson’s, schizophrenia, and depressive disorders, as well as the molecular mechanisms by which neuro- and psychoactive drugs work. The researchers will test the candidate genes’ involvement in Alzheimer’s pathogenesis by analyzing a mice model, and investigate how gene mutations interfere with protein function. The scientists also want to identify the pathways the candidate genes are involved in, a finding that could explain the specific vulnerability of certain neurons.
Impact of Inflammasome Deactivation on Alzheimer’s disease ($75,000)
This research, by Vishwa Deep Dixit, DVM, PhD, a professor of Comparative Medicine and Immunobiology at the Yale School of Medicine, will be an interdisciplinary collaboration with the lab of Dr. Rudy Tanzi, a professor of Neurology at Harvard University and director of the Massachusetts General Hospital Genetics and Aging Research Unit, an eight-laboratory facility where researchers are investigating genetic causes of Alzheimer’s disease.
This study stems from earlier findings that inflammasome activation in microglia controls age-related inflammation in the central nervous system and that CD33-dependent inhibition of amyloid-beta uptake by microglia reduces IL-1 beta (a pro-inflammatory cytokine) to protect against Alzheimer’s. According to the Cure Alzheimer’s release, “Inflammasome is a high molecular weight protein complex that assembles in the cytosol of microglia and myeloid-lineage cells upon encounter with ‘damage-associated molecular patterns,’ such as amyloids, lipotoxic fatty acids or extracellular ATP derived from necrotic cells. Upon assembly, this causes … release of pro-inflammatory cytokines IL-1beta, IL-18 and a special form of cell death called pyroptosis1.”
Nanobodies to Cross the Blood-Brain Barrier ($150,000)
The purpose of this project, by Bart De Strooper, MD, PhD, and Maarten Dewilde, PhD, both with the VIB Center for the Biology of Disease, KY Leuven, is to generate a universal tool that can transport drug molecules to the brain. The vital blood-brain barrier tightly controls which molecules can enter the brain from the bloodstream. As a consequence, most currently available drugs cannot enter the brain, as they must to treat Alzheimer’s disease.
This project, by Huaxi Xu, PhD, of Sanford Burnham Prebys Medical Discovery Institute, will confirm whether SORLA (a sortilin-related endocytic receptor that binds to the amyloid precursor protein) can limit toxic signals from EphA4 (a gene in the nervous system) in response to amyloid beta, and whether molecular strategies to enhance SORLA/EphA4 interactions can further protect neurons from synaptic damage caused by amyloid beta plaque buildup in the brain. Together, this study may provide insight into a new pathway to protect neurons from Abeta damage, and new strategies for improving cognition in Alzheimer’s patients.
Since its founding in 2004, Cure Alzheimer’s Fund has contributed over $45 million to research, funded initiatives that include the important 2014 “Alzheimer’s in a Dish” study. Cure Alzheimer’s notes that 100 percent of funds it raises go directly to research. For more information, visit www.curealz.org
Cure Alzheimer’s Fund