Six Drug Development Projects Awarded Nearly $3 Million By ALS Association


The ALS Association has awarded nearly $3 million to fund six research projects through the Lawrence & Isabel Barnett Drug Development Program.

The grant program, which is named after its founders Lawrence and Isabel Barnett, supports drug discovery research in both academia and industry to develop new drug therapies and test them in a preclinical setting while moving those therapies closer to clinical use.

Since its inception, the program has committed over $10 million to support 32 projects. Of those projects supported by the program 21 have gone on to find partners to take the research forward or attracted follow-on funding from other large funders in government or industry.

“The Lawrence and Isabel Barnett Drug Development Program has fostered critical relationships between academia and industry and helped move the science forward. We are proud of the fact that projects supported by this program have leveraged that support to attract 6 more dollars for every $1 we initially invested,” said Dr. Kuldip Dave, vice president of research at The ALS Association.

Antagonism of RAGE/DIAPH1 and Therapies for Amyotrophic Lateral Sclerosis

A $500,000 grant, supported by a targeted donation from The ALS Association Greater New York Chapter will fund research led by Dr. Anne-Marie Schmidt at NYU Langone Langone Health focused on a novel therapeutic target for ALS, called the Receptor for Advanced Glycation End Products or RAGE. RAGE is expressed in human and murine models of ALS spinal cord and brain and its expression, particularly in glial cells (brain and spinal cord immune-like cells), suggests that RAGE plays pathological roles in ALS by damaging motor neurons and impairing their functions. The group has developed an advanced set of drug-like, small molecule antagonists of RAGE that require final stage refinement for clinical trials and ultimate application. Here, they propose to develop refined therapeutic drug-like small molecule antagonists of RAGE for immediate next steps in clinical development upon completion of this project.

Preclinical evaluation of bemcentinib as a novel therapeutic for ALS

A $500,000 grant will support research led by Dr. Virginia Lee at the University of Pennsylvania. Research undertaken at the University of Pennsylvania Center for Neurodegenerative Disease Research suggests that microglia – key immune cells within the brain – may play an important role in the development and progression of the most common form of ALS. Accordingly, the present study will investigate whether a drug that targets microglia is effective in improving ALS symptoms in mice. Molecular studies will also be undertaken to characterize how the drug works. Positive findings may lead to clinical trials testing this new approach to ALS therapy in human patients.

Development of a matrix metalloproteinase inhibitor for the treatment of ALS

A $500,000 grant will support research led by Dr. Irving Sucholeiki at Aquilus Pharmaceuticals (Aquilus) to preclinically develop a novel inhibitor of a group of proteins that have recently been found to be upregulated in both people with ALS (PALS) and in key mouse models of ALS. Aquilus will complete key animal toxicity and formulation/stability studies necessary before testing the inhibitor in PALS. If the project is successful, Aquilus will be able to complete the majority of the preclinical studies necessary for FDA approval to allow Aquilus to begin clinical testing of this first-in-class experimental therapeutic to treat this devastating disease.

Novel Protein Folding Gene Therapy for ALS

A $500,000 grant sill support research led by Dr. Hishiya Akinori at Sola Biosciences. The company has developed an innovative technology, Engineered Chaperone, that can specifically control the protein folding and protein quality control process such as protein degradation specifically to an intended disease-causing protein. We have demonstrated that Engineered Chaperone therapy targeting TDP-43 (hereinafter referred to as SOL-257) significantly improves protein folding issues associated with TDP-43 in cultured human cells. Experimental mouse expressing mutant TDP-43 develops TDP-43 protein folding issues in conjunction with neurotoxicity, leading to early death. We have further demonstrated that treatment of these mice with SOL-257 attenuated TDP-43 protein folding issues and significantly improved mouse survival. With these milestones, we propose to move forward to test our treatment with SOL-257 in yet another ALS mouse model which is not directly caused by TDP-43 mutation to validate that our therapeutic is potentially effective not only to patients with TDP-43 mutation but also to most of ALS patients who are not directly impacted by TDP-43 mutation. Our goal is to develop our novel treatment using a gene therapy approach, a new modality with huge potential to fight against many diseases.

ASO mediated knockdown of CHMP7 as a novel therapeutic strategy for ALS/FTD

A $494,000 grant provided by The ALS Association Oregon and SW Washington Chapter will support research led by Dr. Jeffrey Rothstein at John Hopkins University. Recent studies indicate that the motor neurons of ALS patients may have problems transporting proteins through the nuclear pore complex (NPC) that serves as a gateway between the nucleus of the cell and the cytoplasm of the cell. These two compartments of the cell, nucleus and cytoplasm, have different functions so if proteins can’t get through the NPC to the correct location then they may not function properly. This NPC dysfunction could contribute to death of motor neurons in ALS. We have shown that the protein CHMP7 appears to play a critical role in the NPC dysfunction that is observed in ALS. Further, we have shown that if we reduce CHMP7 function in cellular models of ALS then measures of NPC function and cellular health are improved. In this project we propose to examine the potential of antisense oligonucleotides (ASOs) targeting CHMP7 as a tool to reduce CHMP7 function in cellular and mouse models of ALS. If successful, our experiments would help to justify further development of ASOs targeting CHMP7 with the ultimate goal of creating a new treatment for ALS.

GLP Studies on Antisense Oligonucleotide Therapies

A $500,000 grant will support research led by Dr. Dan Elbaum at QurAlis, which is developing antisense oligonucleotides (ASOs) that target different disease mechanisms of ALS. The first is a splice switching ASO that corrects a defect caused by TPD43 loss-of-function. The second aims to activate autophagy. These two ASOs require a battery of FDA prescribed toxicological studies before they can enter clinical studies. The toxicological studies will examine the effects of the therapeutic agent on the function of several critical biological systems including cardiovascular and respiratory effects. These essential toxicology assessments will enable these studies to proceed without delay, moving two different but potentially disease modifying therapies forward towards patients with ALS.