Research Spotlight: Laura Ranum, Ph.D., 2022 Clinical Trial Awards Program Recipient

Exciting Research: Investigating Metformin as a Potential Treatment for C9orf72-Linked ALS

Ranum Lab

In a groundbreaking clinical trial, Dr. Laura Ranum and her team at the University of Florida are exploring the therapeutic potential of an unexpected candidate: metformin. Traditionally used to control blood sugar levels in type 2 diabetes patients, metformin’s properties have led researchers to consider it as a potential treatment for familial ALS caused by the C9orf72 gene mutation.

The mutation involves the repetition of six letters of DNA – GGGGCC – leading to the production of toxic proteins called repeat associated non-AUG (RAN) proteins. These rogue proteins aggregate within brain cells, contributing to the development of ALS. Animal models have provided evidence that reducing RAN protein levels can have positive effects on the disease.

Inspired by metformin’s ability to normalize protein production, Dr. Ranum with the help of her lab and Dr. Tao Zu, tested its effects on ALS tissue cultures and mouse models. Promisingly, metformin successfully lowered RAN protein levels and demonstrated improvements in neuroinflammation, behavior, and motor neuron survival.

Based on these encouraging results, Dr. Ranum and her team, in collaboration with esteemed colleagues from the University of Florida, including James Wymer, M.D., Professor of Neurology; Emily Plowman, Ph.D., Associate Professor of Speech, Language, and Hearing Sciences; David Vaillancourt, Ph.D., Professor and Chair of the Department of Applied Physiology and Kinesiology; and Timothy Garrett, Ph.D., Associate Professor of Pathology, Immunology, and Laboratory Medicine, are conducting a small phase 2 open-label clinical trial. Their aim is to investigate the safety and therapeutic potential of metformin for individuals with ALS caused by a mutation in the C9orf72 gene.

The trial’s outcome will be critical in determining the potential of metformin for treating C9orf72-linked ALS. If the results demonstrate a reduction in RAN proteins in cerebral spinal fluid or blood, or improvements in other biomarkers, the next step will involve conducting a larger, multi-center, placebo-controlled trial.

While cautious about metformin’s ability to completely resolve ALS, Dr. Ranum remains hopeful that it could serve as a valuable part of the treatment puzzle. By reducing RAN proteins, metformin may offer a starting point for improvement and further advancements in ALS therapy.

You can check out another article written by ALSA here, We are grateful to the ALS Association and study participants for supporting our clinical trial for C9orf72 ALS patients.

Stay tuned for updates on this exciting research as Dr. Laura Ranum and her team strive to translate laboratory discoveries into potential breakthroughs for ALS treatment. 💪💙 #ALSResearch #ClinicalTrials #HopeForALS

Dr. Ranum’s lab is currently working on new and innovative research every day. Check out Dr. Ranum’s lab page for more information on what they are working on!