Barnett Drug Development Program is Helping Six New Therapies Move Closer to Clinical Trials


We urgently need more and better ALS treatments. Because of this, getting promising therapies out of the laboratory and into clinical testing as quickly as possible is key to making ALS a livable disease.

In this race toward a cure, drug development is like a relay. The first legs generally take place in academic laboratories where scientists make discoveries about what causes ALS, use that knowledge to identify potential new ways to treat the disease, and start testing these approaches in models of ALS.

Then, academic scientists usually pass the baton to scientists at biotech or pharmaceutical companies who work to get a potential treatment ready for clinical trials, conduct those trials, and use the information they’ve gathered to get over the finish line to win Food and Drug Administration approval.

As with any relay, the most precarious step is the handoff. In this case, the transition from the laboratory to the clinic.

Potentially important discoveries often get tripped up by the gap in funding for projects that start the transition from new biological insights into new treatments. Because of that gap, those discoveries can literally get lost in translation.”
Dr. Paul Larkin
Director of Research, the ALS Association

This happens because the research has progressed beyond what is generally funded by traditional academic grants but is seen as too early-stage and risky for industry funding. By supporting projects at this stage through our Lawrence and Isabel Barnett Drug Development Program, we help fill the funding gap and de-risk projects that will attract the attention of pharmaceutical companies and other large investors.

Newly Funded Projects

Over the next 2 years, we will invest more than $2.9 million to support the preclinical assessment of six emerging ALS therapies and help prepare them for clinical testing. These therapies use different approaches to target three important biological mechanisms involved in ALS, providing new opportunities to slow or stop the progression of the disease.

Promoting Autophagy


A nearly universal feature of ALS is the formation of toxic clumps of damaged or misfolded proteins inside motor neurons. Healthy cells are able to break down protein clumps using a cellular recycling system known as autophagy. However, research has shown that this system does not work well in the neurons of people living with ALS. It is thought that increasing autophagy could help reduce toxic protein clumps, which would improve the health of neurons and reduce ALS progression.

One approach being pursued by Coave Therapeutics is to target a protein called transcription factor EB (TFEB), which has recently emerged as a “master activator” of autophagy. With the support of their Barnett Drug Development Award, Director of Translational Science Julien Spatazza, Ph.D., will test whether increasing autophagy using TFEB gene therapy could be a potentially effective treatment for ALS. “By promoting the clearance of accumulated toxic material, we anticipate our approach will halt motor neuron degeneration and preserve muscular function in people with ALS,” he says.

Samsara Therapeutics is developing a more traditional type of drug, known as a small molecule, to enhance autophagy. John Blackwood, Ph.D., who serves as the company’s head of biology, is overseeing the safety and toxicity studies required by regulatory authorities before testing their drug—SAM-001—for the first time in humans. “These experiments will help us reduce risk and maximize success in later clinical trials,” he says.

Inhibiting HDAC6

Neuron cells

Another factor linked to the clumping of damaged or misfolded proteins is an enzyme called HDAC6. HDAC6 has also been shown to play a role in regulating the system that transports proteins from one part of a neuron to another. Because both these processes are thought to be involved in ALS, blocking the action of HDAC6 is seen as a promising way to protect against neuron loss and damage by two of our Barnett Drug Development Grant recipients.

Augustine Therapeutics is developing a new class of selective HDAC6 inhibitors. Under the direction of Frederik Rombouts, Ph.D., the company’s head of medicinal chemistry, the aim of the funded project is to perform an extended set of biology, pharmacology, safety, and toxicity tests to select the best representative of this new class of drugs for future studies.

Oryzon Genomics has developed an HDAC6 inhibitor called ORY-4001. With their grant, which was supported by a generous donation from the Koorsen Family Charitable Fund, Oryzon’s Chief Scientific Officer Jordi Xaus, Ph.D., is seeking to better understand ORY-4001’s safety and efficacy in models of ALS. ​“If these preclinical results are positive, we plan to extend the clinical development of ORY-4001, now in [Charcot-Marie Tooth (CMT) type 1], to include ALS and explore its therapeutical potential for people living with this devastating disease,” he says.

Targeting Inflammation

Test tubes

A growing number of studies have implicated inflammation in the central nervous system as a key factor driving ALS. Inflammation occurs when the immune system sends out cells to fight bacteria or clean up damaged or injured tissue. In people living with ALS, changes in neurons appear to over-activate immune cells, so two of our awardees are interested in seeing if targeting a specialized type of immune cell in the central nervous system called microglia could help reduce symptoms of the disease.

Myrobalan Therapeutics has developed an oral drug called a CSF1R inhibitor that helps reduce the number of microglia. With the support of the Barnett Drug Development Program, Principal Investigator Michael Young, Ph.D., will conduct the additional preclinical research needed to prepare Myrobalan’s CSF1R inhibitor for first-in-human studies. “This funding will provide crucial insights that will inform clinical trial design to rapidly address the unmet needs of people with ALS,” he says.

Howard Weiner, M.D., co-director of the Center for Neurologic Diseases at the Brigham & Women’s Hospital, is using a different strategy to help decrease inflammation and normalize microglia in the central nervous system—a monoclonal antibody that targets an inflammatory protein complex called CD3 and is delivered through the nose. With his award, Dr. Weiner plans to better understand how the treatment works in the body and identify the best dosing regimen for clinical studies.

Thanks to the ongoing generosity of the Barnett Family Foundation and the support of the Koorsen Family Charitable Fund and our donors, we are continuing to accelerate progress in the search for treatments and cures so ALS will be livable for everyone, everywhere.

If you would like to receive monthly ALS research updates, SUBSCRIBE to our newsletter, Research Matters. To learn more about how you can get involved in the fight against ALS, visit our website HERE.

To continue to follow stories about people living with ALS in the community and learn more about the disease, follow our blog HERE.


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