Overview
Beyond excellent clinical care of patients suffering from degenerative brain diseases, part of the mission of the Cleveland Clinic Lou Ruvo Center for Brain Health is to innovate to advance healthcare. One goal is to repurpose drugs already approved or developed for other conditions toward the treatment of neurodegenerative disease. Testing of repurposed agents is important because the side effect profile and pharmacokinetics are well understood, allowing effective agents to be brought to the market more rapidly than new agents.
Currently, we have identified three such drugs and are testing their efficacy in treating neurodegenerative disorders in clinical trials at the Lou Ruvo Center for Brain Health.
- Rasagaline inhibits an enzyme called monoamine oxidase and is approved for the treatment of Parkinson’s disease. Research at LRBCH has suggested that Rasagaline might be useful to treat Alzheimer’s disease (AD). Through a grant from the Alzheimer’s Drug Discovery Foundation, a clinical trial is underway to investigate the effect of Rasagaline on the progression of AD symptoms.
- Bexerotene is an anti-cancer agent approved by the U.S. Food and Drug Administration (FDA) (in late 1999) and the European Medicines Agency (EMA) (early 2001) for use as a treatment for certain types of lymphoma. Research at the Lou Ruvo Center for Brain Health has shown that Bexerotene might be a potent treatment for AD and could even alter the extent of pathology in the brains of AD patients, as detected on brain scans. Further studies are being planned.
- Lenalidomide (Revlimid®) was first approved in 2006 for use in patients with multiple myeloma. In February 2017, Lenalidomide monotherapy was approved in the U.S. for maintenance treatment after autologous stem cell transplantation in patients with newly diagnosed multiple myeloma (Syed, 2017). Lenalidomide inhibits TNF-α production, stimulates T cells, and has immunomodulatory, anti-inflammatory, and anti-neoplastic effects. It also reduces levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and inhibits angiogenesis (NCI Thesaurus). It is a thalidomide analogue with improved potency and reduced toxicity compared to thalidomide. Two clinical trials are being launched to investigate the effects of Lenalidomide in the treatment of mild cognitive impairment as a prodrome of AD. These trials will be launched in early 2020.
Publications
Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial. Decourt B, Drumm-Gurnee D, Wilson J, Jacobson S, Belden C, Sirrel S, Ahmadi M, Shill H, Powell J, Walker A, Gonzales A, Macias M, Sabbagh MN. Curr Alzheimer Res. 2017;14(4):403-411. doi: 10.2174/1567205014666170117141330. PMID: 28124585
Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease. Cummings JL1, Zhong K2, Kinney JW3, Heaney C4, Moll-Tudla J5, Joshi A6, Pontecorvo M7, Devous M8, Tang A9, Bena J10. Alzheimers Res Ther. 2016 Jan 29;8:4. doi: 10.1186/s13195-016-0173-2. PMID: 26822146
Repackaging FDA-approved drugs for degenerative diseases: promises and challenges. Cummings JL, Zhong K. Expert Rev Clin Pharmacol. 2014 Mar;7(2):161-5. doi: 10.1586/17512433.2014.884923. Epub 2014 Feb 6. PMID: 24502586
A review: treatment of Alzheimer's disease discovered in repurposed agents. Appleby BS, Nacopoulos D, Milano N, Zhong K, Cummings JL. Dement Geriatr Cogn Disord. 2013;35(1-2):1-22. doi: 10.1159/000345791. Epub 2013 Jan 9. PMID: 23307039
Why do trials for Alzheimer's disease drugs keep failing? A discontinued drug perspective for 2010-2015. Mehta D, Jackson R, Paul G, Shi J, Sabbagh M. Expert Opin Investig Drugs. 2017 Jun;26(6):735-739. doi: 10.1080/13543784.2017.1323868. PMID: 28460541
Members & Collaborations
Cleveland Clinic Affiliations
External Relationships and Collaborations
- Jefferson Kinney, PhD, University of Nevada Las Vegas
