Grants of $4.6M to Support Trials of Cancer Therapy in Early Alzheimer’s

The National Institute of Aging (NIA) and the Alzheimer’s Drug Discovery Foundation (ADDF) have awarded $4.6 million to a team of researchers studying the potential of the cancer therapy Revlimid (lenalidomide) in treating people with early stage Alzheimer’s disease.

Two clinical trials, each supported by one of these grants, are planned. The first is now recruiting up to 30 eligible adults at its single site in Nevada.

The $3.2 million grant from the NIA — a branch of the National Institutes of Health — and the $1.4 million grant from ADDF were given to a research team led by Marwan Sabbagh, MD, and Boris Decourt, PhD, of the Cleveland Clinic Lou Ruvo Center for Brain Health. Both grants run for five years.

“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,” Sabbagh, the center’s director, said in a press release.

Revlimid is an FDA-approved immunomodulatory treatment developed by Celgene (part of Bristol Myers Squibb) to treat blood cancers, such as multiple myeloma. It targets cells by binding to a specific protein called cereblon, which is involved in regulating the activity of proteins related to cell adhesion, metabolism, and division.

By binding to cereblon, Revlimid triggers the death of cancer cells by affecting these processes.

Revlimid also works as an immunomodulatory therapy, meaning it is capable of modifying and regulating certain immune system functions. It also blocks the formation of new blood vessels around tumors, preventing their growth.

“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,” Sabbagh said.

The research project, “Repurposing Lenalidomide for Early Alzheimer’s Treatment,” is divided in two complementary clinical trials that aim to determine if Revlimid is safe, and if can reduce inflammation and disease biomarkers while improving cognition in patients with early stage Alzheimer’s.

The first Phase 2 trial (NCT04032626), named MCLENA-1 and sponsored by the Cleveland Clinic in cooperation with the NIA, will evaluate the safety, tolerability, and efficacy of long-term treatment with lenalidomide (10 mg daily, taken orally) compared to a placebo.

The study will include 30 patients, ages 50 to 89, with mild cognitive impairment (MCI) — a neurological condition marked by subtle changes in memory — due to Alzheimer’s.

Treatment will last for one year, followed by a six-month washout period. The trial’s primary goal is to assess lenalidomide’s effect on cognition. Secondary goals include evaluating treatment safety and tolerability, as well as change in the levels of brain amyloid, neurodegeneration and blood inflammatory biomarkers.

The trial is currently recruiting patients at the Cleveland Clinic Lou Ruvo Center for Brain Health, in Las Vegas.

The second study, supported by the ADDF, will also be a Phase 2 trial to evaluate the safety and effects of short-term treatment with lenalidomide in 45 patients with MCI.

In this study, patients will be randomly assigned to either lenalidomide (5 mg daily) or a placebo for six months, followed by one month washout.

Researchers will measure lenalidomide’s effects on biomarkers in blood and cerebrospinal fluid, the liquid surrounding the brain and spinal cord.