The Alzheimer's Drug Discovery Foundation (ADDF) announces $7.1 million in new funding to date this year. These seven investments reflect the ADDF's robust strategy to advance drug discovery and clinical trials, including the development of biomarkers for early detection/diagnostics and prevention methods.
"This is an exciting time in Alzheimer's research because we know so much more about the disease," noted Dr. Howard Fillit, Founding Executive Director and Chief Science Officer of the ADDF. "We continue to pursue and push every viable avenue to accelerate this understanding and bring effective medications to patients for the treatment and prevention of Alzheimer's."
Susan Catalano, PhD, Cognition Therapeutics, Inc.
SHINE (Study Synaptic Health and Improvement of Neurological Function with Elayta): A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial
The loss of synapses, which permit communication between nerve cells, is strongly correlated to cognitive decline. Growing evidence suggests that synaptic dysfunction is one of the primary drivers of Alzheimer's disease. Cognition Therapeutics has developed a candidate drug, Elayta, that works through a novel mechanism to stop the binding of toxic proteins that build up in the brain and damage synapses. Elayta was shown to be safe in phase 1 trials and is now being tested in phase 2 clinical studies in patients with mild to moderate Alzheimer's disease, supported in part by an NIH grant.
A critical component of these trials is to measure the drug’s effects on levels of toxic proteins and markers of synaptic damage. ADDF funding will allow for the inclusion of these endpoints in the trials and answer important questions about how the drug is working in their target patient population. ADDF funding will also support the manufacturing of additional drug quantities that were not covered by NIH funding.
Marwan Sabbagh, MD, Cleveland Clinic Lou Ruvo Center for Brain Health
Repurposing Lenalidomide for Early Alzheimer's Treatment
Inflammation is pervasive to many neurological disorders and is now thought to play an important role in Alzheimer's disease. Dr. Sabbagh and his team are interested in drugs that lower brain inflammation with the goal of preventing or slowing down progression to Alzheimer's disease. In their phase 1b/2a trial, they will study an anti-cancer drug, called lenalidomide, in people with mild cognitive impairment (MCI). Lenalidomide significantly reduced inflammation and biomarkers, including amyloid plaques, in animal models. Because lenalidomide has never been tested in the context of Alzheimer’s, Dr. Sabbagh will monitor carefully the safety and tolerability in MCI patients, as well as whether the drug modulates inflammation using inflammatory markers in blood.
Linda Van Eldik, PhD, University of Kentucky Research Foundation
Phase 2 Enabling Toxicology Studies of MW151, A Selective Small Molecule Suppressor of Neuroinflammation for Alzheimer's Disease
The brain's immune cells normally protect it from possible sources of danger like toxins or amyloid plaques by becoming activated and removing the sources. During activation, chemical signals called proinflammatory cytokines are released. However, with chronic inflammation, these cells overproduce these cytokines, which can damage nerve cells and lead to cognitive decline. Dr. Van Eldik has developed a novel, small molecule drug called MW 151 that selectively suppresses proinflammatory cytokine overproduction and rescues nerve cell damage and cognitive impairment in many different animal models. It is currently being tested in phase 1 safety trials. The current project will run in parallel with the ongoing phase 1 study and will test MW 151 in toxicology studies required by the FDA for longer-term dosing in a phase 2 study. ADDF funding will enable Dr. Van Eldik's team to move into phase 2 trials in patients after the phase 1 study is completed.
Kevin Hodgetts, PhD, The Laboratory for Drug Discovery in Neurodegeneration at Brigham and Women's Hospital and Harvard Medical School
Novel Benzoxazines for the Treatment of Alzheimer's Disease
This project will be funded as part of the ADDF's established, longstanding partnership with the Harrington Discovery Institute (HDI).
Dr. Hodgetts has been selected as the 2018 ADDF-Harrington Scholar. In addition to receiving ADDF funding, he will be supported by a team of drug development experts provided by the Harrington Discovery Institute. These experts have significant experience in commercial drug development and established networks that will help guide Dr. Hodgetts' program towards success.
Dr. Hodgetts has identified a drug that reduces inflammation and increases the synthesis of a protective neurosteroid in the brains of animal models of neurodegeneration. However, the drug needs to be further optimized to improve its therapeutic efficacy and stability in humans. Dr. Hodgetts will work closely with Harrington advisors to develop an improved analog that is suitable for further clinical development.
Joel Dudley, PhD, Icahn School of Medicine at Mount Sinai
Deep Learning to Unveil Neurological Disorder Patterns and Novel Therapeutics from the Electronic Health Records
Dr. Dudley and his team will use sophisticated computational methods to develop predictive models in order to identify currently FDA-approved medications that could be repurposed for Alzheimer's. They will apply artificial intelligence methods to mine electronic health records of the Mount Sinai Health System, which contains massive amounts of clinical data on over 6 million patients. In 12 months, this project will identify currently approved medications associated with a decreased risk for cognitive decline and dementia that should be studied in clinical trials for the treatment of Alzheimer's.
Hussein Yassine, MD, University of Southern California
Effect of Early Supplementation with High Dose DHA on Cognitive Outcomes in APOE4 Carriers: "PreventE4 Trial"
DHA, an omega 3 fatty acid found in fish, is a supplement available at any vitamin or drug store. Dr. Yassine and his team will test if a high dose of DHA can prevent cognitive decline in individuals with APOE4, which is the greatest genetic risk factor for Alzheimer's disease. Previous clinical trials suggest that DHA is not effective in APOE4 patients who were already diagnosed with Alzheimer’s but may be effective in individuals before they show signs of the disease. Dr. Yassine will treat 160 participants, ages 60-80, with normal cognition but at least one cardiovascular-related dementia risk factor (e.g. high blood pressure, high cholesterol, etc.) with 2 grams of DHA or placebo per day for two years to see if it improves memory. Half of the individuals will be APOE4 carriers. Dr. Yassine is currently funded by the NIH to treat 160 participants with DHA to see how much gets into the brain. ADDF funding will add an additional 160 to the ongoing study, bringing the total number to 320. This will allow Dr. Yassine and colleagues to see whether DHA preserves memory function and brain structure.
Rosa Canet-Aviles, PhD, Foundation for the National Institutes of Health (NIH)
ADNI-3 (Alzheimer's Disease Neuroimaging Initiative)
ADNI is conducted by the National Institute on Aging (NIA) and is the NIH's largest public-private partnership on brain research to date, funded by two non-profits (including the ADDF), 20 companies, and the NIA. This landmark study is currently housed at 59 clinical sites in the United States and Canada. This study was designed to develop methods, acquire data, and form a collaborative network of clinical and imaging sites to facilitate the use and evaluation of neuroimaging and other biomarkers in clinical trials for Alzheimer's disease. ADNI-3, which builds on first and second study phases, seeks to identify the earliest changes in brain structure and function as people transition from normal cognitive aging to mild cognitive impairment and early Alzheimer's disease. The current add-on funding will support the analysis of cerebral blood flow in brain measured by PET imaging in 100 study participants over two years.