Cleveland Clinic receives two grants to study therapeutic potential of anti-cancer drug in Alzheimer's

The National Institute of Aging (NIA), part of the National Institutes of Health (NIH), and the Alzheimer's Drug Discovery Foundation (ADDF) awarded five-year grants of $3.2 million and $1.4 million, respectively, to scientists from Cleveland Clinic Lou Ruvo Center for Brain Health to study the therapeutic potential of the anti-cancer drug lenalidomide in early-stage Alzheimer's disease, known as mild cognitive impairment (MCI).

The funding will support the project "Repurposing Lenalidomide for Early Alzheimer's Treatment" led by Marwan Sabbagh, M.D., and Boris Decourt, Ph.D., of the Lou Ruvo Center for Brain Health. The project is comprised of two complementary clinical studies aimed at identifying whether lenalidomide reduces inflammation and other disease-related neuropathological features, and improves cognition in those living with mild cognitive impairment.

Enthusiasm to study lenalidomide stems from the strategy to target multiple Alzheimer's disease neuropathologies at once, a relatively new approach in Alzheimer's disease drug development. Lenalidomide is one of few multi-purpose agents, which has demonstrated several effects on the immune system in cancer patients. Additionally, as an FDA-approved drug, lenalidomide's safety and toxicity profiles have already been established, which will help accelerate testing and progression in Alzheimer's clinical studies if the present project is successful.

To date, disease-modifying therapies have only used a single drug approach to target Alzheimer's disease pathologies, and they have all failed. These grants will help us explore a novel approach in reducing several pathologies simultaneously. With its dual mechanistic nature, lenalidomide is particularly intriguing because it has the potential to both reduce chronic inflammation and lower amyloid beta loads in the brain, which are both indicators of Alzheimer's disease."

Dr. Marwan Sabbagh, Director, Lou Ruvo Center for Brain Health

The two lenalidomide sister studies will recruit participants with early-stage Alzheimer's disease/MCI at the Lou Ruvo Center for Brain Health. The first study is funded by the NIH and is a 20-month Phase II investigation evaluating the effect of long-term use of lenalidomide on cognition, along with safety and tolerability.

The second study, supported by ADDF funding, is a six-month Phase II investigation examining the short-term use of lenalidomide in 45 participants, with a focus on safety and effects on blood and cerebrospinal fluid biomarkers. Dr. Sabbagh's work is also supported by the Camille and Larry Ruvo Endowed Chair for Brain Health.