There is an urgent need for new and improved therapies for ALS, as there is still no cure. To help expand the drug development pipeline, we are proud to support the preclinical assessment of emerging ALS therapies through The Lawrence and Isabel Barnett Drug Development Program.

Through this program, we award researchers with up to $500,000 over two years to fund the preclinical assessment of new and repurposed ALS therapies in preparation for clinical testing. This program prioritizes projects that have a high probability of reaching the clinic within three years.

The four grants awarded during the 2022 funding cycle support investigations into several therapeutic approaches targeting a diverse set of biological pathways shown to underlie the development and progression of ALS. 

Sapan Gandhi, Ph.D.

Chief Technology Officer, Drishti Discoveries Ltd

This $500,000 grant funds research into a proprietary microRNA-adapted short hairpin RNA technology the company has developed for ALS. In an estimated 97% of people with ALS, the protein TDP-43 clumps inside brain or nerve cells, setting off a cascade of events that causes these cells to die. Due to its essential function, targeting TDP-43 directly is not a feasible treatment strategy. However, targeting genetic modifiers of TDP-43 toxicity, such as the ATXN2 (ataxin-2) gene, offers a viable therapeutic approach. With this project, Gandhi and co-principal investigators Pamela Shaw, M.D., and Richard Mead, Ph.D., are aiming to confirm the ability of the technology to significantly silence the ATXN2 gene and preserve motor function in ALS mouse models in the pursuit of developing a long-term treatment for ALS. The project will be carried out in collaboration with the Sheffield Institute for Translational Neuroscience, UK.

Martin Gill, Ph.D.

Vice President and Head of Biology, Libra Therapeutics, Inc.

Dr. Gill was awarded $450,272 to investigate whether small molecule activation of TRPML1 is beneficial in pre-clinical models of ALS. TRPML1 is a channel located on lysosomes, which are the key cellular compartments where “cellular trash” is degraded. This degradation process in lysosomes is impaired in the brains and spinal cords of people with ALS. Small molecule activation of TRPML1 has been shown to increase lysosome number and function in cells. As part of this project, the researchers will investigate whether small molecule activation of TRPML1 increases lysosomal signaling and function in animals. They, then, will seek to determine how much TRPML1 activation is needed to produce beneficial effects in pre-clinical animal models of ALS. Additionally, this funding will support identification and early biomarker of biomarkers related to lysosome number and function for use in future clinical trials.

Justin Ichida, Ph.D.

John Douglas French Alzheimer’s Foundation Endowed Associate Professor of Stem Cell Biology and Regenerative Medicine, University of Southern California

This $500,000 grant supports the development of an antisense oligonucleotide that targets the RNA splicing/export factor SYF2. Antisense technology is a way to prevent the production of proteins involved in disease. Preliminary data from the Ichida Lab showed that suppressing SYF2 in ALS disease models reduced the buildup of TDP-43 aggregates in neurons and improved TDP-43 activity. This foundational work was conducted by Yichen Li, Ph.D., co-principal investigator of this project, and funded by a 2020 Milton Safenowitz Postdoctoral Fellowship. With this new project, the researchers are seeking to validate the efficacy of suppressing SYF2 with antisense oligonucleotides for both genetic and sporadic forms of ALS as well as to select a lead antisense oligonucleotide for clinical development.

Kim Staats, Ph.D.

Scientific Advisor to Raya Therapeutic, Inc.

This $150,000 grant supports testing a combination of two new oral small molecules that have the potential to address multiple ALS disease mechanisms simultaneously and target multiple cell types to protect motor neurons. The study will use motor neurons and other cell cultures to determine the best concentrations and ratios of the drugs to use together. Both drugs have been tested in clinical trials in the past (not in ALS) and have favorable safety profiles.