People living with ALS urgently need new treatments, so getting promising potential therapies out of the laboratory and into clinical testing as quickly as possible is essential.

To help accelerate this crucial transition, we have awarded five new grants through our Lawrence and Isabel Barnett Drug Development Program. These grants—totaling $2.2 million dollars over the next two years—will support the continued preclinical development of five emerging ALS therapies in preparation for clinical testing.

“To truly make ALS a livable disease, we need treatments that help people breathe better, that help them continue to be able to speak and eat, that help them remain independent, and that ultimately help them live longer,” said Dr. Kuldip Dave, senior vice president of research at the ALS Association.

The five projects selected for funding target a variety of important biological processes and pathways involved in ALS, providing new hope for slowing or stopping progression of the disease.

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Evaluation of Pharmacological Modulation of SARM1 by ASHA-624

Bradlee Heckmann, Ph.D.​, president and chief scientific officer at Asha Therapeutics​, is leading the development of a novel therapy called ASHA-624 that specifically binds to and inhibits SARM1, a protein known to drive neuron degeneration. By inactivating SARM1, ASHA-624 has been shown in preliminary preclinical studies to stop damage to neurons and muscles. “Funding through the Barnett grant will provide key foundational data for our upcoming transition into clinical trials and support patient enrollment and identification,” he said. Learn more about this project.

Inhibition of P2X7R for the Treatment of ALS

Michael Kassiou, Ph.D.​, a professor of medicinal chemistry at The University​ of Sydney​, aims to “make a significant impact by validating specific drivers of neuroinflammation as legitimate therapeutic targets for ALS.” He plans to do this by focusing on a drug that blocks a receptor called P2X7 that is primarily found on immune cells, including those found within the central nervous system. Dr. Kassiou hopes the results of this funded project will not only “increase our understanding of the disease but also attempt to translate scientific discoveries into effective therapies for those suffering from this debilitating condition.” Learn more about this project.

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Development of a Highly Brain Penetrant CSF1R Inhibitor

Ryan Lim, Ph.D.​, director of biology at Modulo Bio, is furthering the development of a drug that blocks a protein called the colony stimulating factor 1 receptor (CSF1R). Blocking CSF1R helps reprogram microglia, the brain's immune cells, to protect neurons from damage. According to the company, “if successful, this could slow or even stop disease advancement. For ALS patients and their families, slowing the disease's progression could mean additional years of independence and quality time together.” Learn more about this project.

Evaluation of Novel Inhibitors of the Mitochondrial Permeability Transition Pore​ (mPTP)

Richard Rutter, Ph.D.​, co-founder and chief scientific officer of NRG Therapeutics​, is investigating a new class of potential ALS drugs that could help protect mitochondria. Mitochondria act as “batteries” within cells, supplying them with energy, and are especially important for maintaining the health of brain cells. This project will help the company determine how much of the drug needs to be given to clinical trial participants. “We are excited about the therapeutic potential of our novel CNS-penetrant mPTP inhibitors in ALS and other neurodegenerative diseases and look forward to progressing our lead compound into the clinic in 2025,” Dr. Rutter said. Learn more about this project.

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Human-Derived TDP-43 Intrabodies to Restore TDP-43 Function in ALS

Nikole Zuniga Quiroz, Ph.D.​, a scientist at Mabylon AG​, is advancing the development of a new gene therapy approach that targets toxic tangles of the protein TDP-43, which are found in more than 90% of people with ALS (both sporadic and genetic forms of the disease). “Leveraging our antibody engineering unique know-how, we developed a novel concept: intrabodies delivered directly to neurons to fight TDP-43 toxicity from within the cell,” Dr. Zuniga Quiroz said. “Demonstrating in vivo preclinical efficacy with this funding will allow us to proceed with all the necessary steps to bring this potential treatment to patients as soon as possible.” Learn more about this project.

Accelerating New Treatments by Bridging a Gap in Funding

Many potential new therapies stall in the late stages of preclinical development due to a lack of funding. These projects have often progressed past the point typically supported by academic grants, but they are often seen as too early-stage and risky for industry investment.

“IND [investigational new drug]-enabling studies are a critical step that often struggles to attract traditional venture capital,” explained Michael Horowitz, CEO and co-founder of Modulo Bio. “The ALS Association's support at this stage bridges a crucial gap, allowing us to generate the rigorous scientific and regulatory data needed to advance our program toward a new treatment option for people living with ALS.”

Thanks to the ongoing generosity of the Barnett Family Foundation and other donors, we have now committed over $17 million to support 47 drug development projects. Approximately 60% of our Barnett Drug Development Program awardees have gone on to establish partnerships to help advance their research, received larger grants from places like the National Institutes of Health and the Department of Defense ALS Research Program, and/or attracted commercial support from pharmaceutical/biotech companies or venture capitalists. In addition, at least nine projects have moved forward into clinical trials.

“Support at this juncture is not just appreciated, it's transformative, especially for innovative small biotech companies like ours,” Dr. Zuñiga Quiroz said. “We can have great ideas within a small, dedicated team, but without your help, our candidate molecule might be left on the bench. Your belief in our project has provided us with more than just financial means, it has given us the opportunity to potentially transform a promising idea into a life-changing therapy.”

More information about the drug development process can be found on our website HERE. 

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