Two-year NIH grant awarded to WMed will fund Dr. Thomas L. Rothstein’s study of ALS

Thomas L. Rothstein, MD, PhD
Thomas L. Rothstein, MD, PhD

The medical school has been awarded a two-year, $415,250 grant from the National Institutes of Health (NIH) that will fund important research focused on the treatment and prevention of Amyotrophic Lateral Sclerosis (ALS).

The research project, “FAIM Proteostasis in ALS,” is being led by Thomas L. Rothstein, MD, PhD, who serves as chair of the Department of Investigative Medicine and leads the Center for Immunobiology at WMed. The NIH funding includes $275,000 for direct costs.

The project builds on more than 25 years of research by Dr. Rothstein that has examined how Fas Apoptosis Inhibitory Molecule (FAIM) functions in immune cells.  FAIM protect cells from stress-induced death by preventing protein aggregation.

As it relates to ALS, also known as Lou Gehrig’s Disease, Dr. Rothstein and his team of researchers, including Hiroaki Kaku, PhD, have shown that FAIM counteracts the intracellular accumulation of mutant protein aggregates identified in familial forms of ALS and promotes proteostasis of an aggregation-prone ALS protein.

Now, with the new funding from the NIH, Dr. Rothstein said his team will conduct experiments using neurons derived from human induced pluripotent stem cells and mouse models if ALS disease to determine whether – and how – FAIM inhibits protein aggregation in neuronal cells and to what extent FAIM affects disease in a preclinical model. The answers to these questions, he said, could potentially hold the key to future treatments for – and the prevention of – ALS, which causes the deterioration of motor neurons and leads to invariably fatal muscle weakness.

The work is part of several ongoing research projects within the Center for Immunobiology that are specifically probing the role of FAIM in neurodegenerative diseases like ALS, Alzheimer’s disease, and Parkinson’s disease.

Dr. Kaku, a research assistant professor in the Department of Investigative Medicine, is leading a project, “Understanding the link between FAIM expression and Alzheimer’s disease and related dementias,” that was awarded a two-year, $151,000 grant from the NIH in 2021. Prior to that, Dr. Kaku also received a $200,000 grant from a private foundation for a similar project exploring the role of FAIM in Parkinson’s disease.

Dr. Rothstein said he is hopeful that the experiments he and his team will conduct to better understand the role of FAIM in ALS may lead to future breakthroughs in the treatment and prevention of the deadly disease.

“This is one of those things where we’ve followed the data,” he said. “Now, we’ll learn whether FAIM’s activity against protein aggregation occurs in neuronal cells and that’s something we’ve never had a chance to look at before.”