by Bill Snyder
Vanderbilt University Medical Center is partnering with Evergreen Therapeutics Inc. to test whether an Alzheimer’s drug, memantine, can improve cognitive symptoms associated with systemic lupus erythematosus (SLE), an autoimmune disease.
The external licensing and clinical trial agreement to “repurpose” a drug already on the market for a new use, signed last month, is a first for the Drug Repurposing Program of the Vanderbilt Institute for Clinical and Translational Research (VICTR).
Established in 2016, the Drug Repurposing Program currently is recruiting subjects for five clinical trials, including the memantine study. In July 2022, VUMC announced its intention to collaborate with a not-for-profit social impact organization, Roivant Social Ventures, to develop therapies for traditionally underserved populations and diseases.
To find new uses for drugs already on the market, the drug repurposing team identifies variants in drug gene targets and conducts PheWAS (phenome-wide association studies) and comprehensive literature evidence synthesis.
PheWAS was developed at VUMC using the de-identified electronic health records (EHRs) of hundreds of thousands of patients that have been linked to genetic data stored in BioVU, VUMC’s biorepository.
Memantine is used to treat moderate-to-severe confusion (dementia) associated with Alzheimer’s disease.
It targets a gene called GRIN2a, which encodes a receptor protein in the brain thought to be important in learning and memory.
When PheWAS analysis was conducted for variants in the memantine-target gene GRIN2a, it identified a novel association with SLE, commonly called lupus.
Manual literature searches and physician chart reviews conducted by VUMC lupus expert April Barnado, MD, MSCI, assistant professor of Medicine and Biomedical Informatics, suggested that memantine might be effective for lupus patients suffering from neurocognitive symptoms. To prove it, a clinical trial would need to be conducted.
“There is a vast number of strategies and models to generate drug repurposing hypotheses; however, FDA approvals for new indications for repurposed drugs are scarce,” said VICTR executive director Jill Pulley, MBA.
“The limited success in the repurposing world to date demonstrates that the findings generated via these predictive models must be validated in human clinical trials to prove utility,” Pulley said.
That is where Evergreen Therapeutics comes in. Established in 2019 and based in Bethesda, Maryland, Evergreen Therapeutics focuses on the research and development of innovative drugs in autoimmunity and ophthalmology, among other fields, with an emphasis on finding new indications for existing drugs to tackle unmet clinical needs.
“We’re very pleased with the SLE collaboration with Vanderbilt University Medical Center, a renowned medical center recognized worldwide,” said Xin Du, PhD, Evergreen Therapeutics’ chief executive officer.
“Utilizing Evergreen Therapeutics’ end-to-end AI (artificial intelligence) drug development platform and strong clinical and regulatory expertise, we are committed to identify therapeutic agents for diseases without approved treatments,” he said. “Together with VUMC, we will work hard to bring new treatments to SLE patients with cognitive impairment safely and quickly.”
Evergreen Therapeutics will work together with VUMC to conduct the clinical trial of memantine to treat cognitive impairment in about 60 adult patients with lupus at VUMC and other to-be-determined trial sites.
Leslie Crofford, MD, professor and director of the Division of Rheumatology and Immunology at VUMC, who holds the Wilson Family Chair in Medicine, is the study’s principal investigator.
Participants in the 14-week, double-blind “ClearMEMory” trial will be randomized to receive memantine or inactive placebo.
“The long-term goal of the program is to develop and make available a safe and affordable therapeutic approach to reduce debilitating cognitive symptoms in a precisely selected lupus sub-population,” Crofford said.
Others from VUMC on the study team include:
- Clinical Psychologist and Research Professor James Jackson, PsyD, co-principal investigator of the trial.
- Sharon Philips, MSPH, associate in Biostatistics and Lead Study Statistician.
- Erin Collar, MPH, assistant lead in the Long-term Outcomes Core of the Critical Illness, Brain Dysfunction and Survivorship Center.
- Jillian Rhoads, PhD, senior scientific project manager, VICTR.
- Jon Williams, PhD, Division of Rheumatology and Immunology, lead study coordinator.
