Healey & AMG Center for ALS announces new drug regimen for testing DNL343 in HEALEY ALS Platform Trial

The HEALEY ALS Platform Trial is adding a new investigational drug, DNL343, to continue to research new treatments for ALS (Amyotrophic Lateral Sclerosis or Lou Gehrig’s disease).

The trial, led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital in collaboration with the Northeast ALS Consortium (NEALS), is a trial in which multiple investigational drugs are tested and evaluated simultaneously to accelerate the development of potential new ALS therapies. Drug candidates that enter the platform trial are chosen by a group of expert ALS scientists and members of the Healey & AMG Center Science Advisory Committee.

DNL343 targets eIF2B, a key regulator of the integrated stress response (ISR). In neurons exposed to cellular stressors, inhibition of the ISR by DNL343 restores protein synthesis and dissolves pre-formed TDP-43 containing stress granules. This effect of DNL343 is of clinical interest because TDP-43 containing stress granules are thought to lead to TDP-43 inclusions, a hallmark of ALS pathology. DNL343 is being developed by Denali Therapeutics, a publicly owned biotechnology company based in South San Francisco, CA, and is not yet approved for use in any country. The Healey & AMG Center for ALS at Mass General and Denali Therapeutics recently signed an agreement to work together to design a trial of DNL343 in the HEALEY ALS Platform Trial.

“We are thrilled to be testing DNL343 in the HEALEY ALS Platform Trial,” says Merit Cudkowicz, MD, MSc, principal investigator and sponsor of the HEALEY ALS Platform Trial, director of the Sean M. Healey & AMG Center for ALS, chief of the Department of Neurology at MGH, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “The drug was selected by an expert committee based on strong science. By adding one more drug to the platform, we continue to push research forward in hopes of soon finding many more effective treatments for ALS.”

“The HEALEY ALS Platform Trial is a large-scale collaborative effort made possible by contributions from patients and families, clinical trial sites, industry partners and research collaborators and by funding from the Healey & AMG Center, Tackle ALS, The ALS Association, ALS Finding A Cure, ALS One, Muscular Dystrophy Association, I AM ALS, and Tambourine,” says Sabrina Paganoni, MD, PhD, co-principal investigator of the trial, physician scientist at the Healey & AMG Center, and Associate Professor of PM&R at Harvard Medical School. “In addition to testing multiple investigational drugs, the trial is producing a wealth of data, samples, and tools to better understand ALS and to continue to advance the field of ALS clinical trials.”

The platform trial has been testing several other investigational drugs. Testing of pridopidine, an oral, highly selective Sigma-1 receptor (S1R) agonist, and trehalose, a low molecular weight disaccharide that affects autophagy and lysosomal pathways, is ongoing and more investigational drugs are scheduled to be added over the next few months.

Background on ALS

Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide. ALS causes the progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy. There are currently few FDA therapies approved for treating ALS—riluzole, edaravone (IV and oral formulation), Relyvrio, and Nuedexta.

About the Sean M. Healey & AMG Center for ALS at Mass General

At the Sean M. Healey & AMG Center for ALS at Mass General, we are on a quest to discover life-saving therapies for all individuals affected by ALS. Launched in November 2018, the Healey Center leverages a global network of scientists, physicians, nurses, caregivers, people with ALS and families working together to accelerate the pace of ALS therapy discovery and development.

Under the leadership of Merit Cudkowicz, MD and a Science Advisory Council of international experts, we are reimagining how to develop and test the most effective therapies to treat the disease, identify cures and, ultimately, prevent it.

The key to our success is our tightly integrated research and clinical efforts, encouraging opportunities to bring the challenges our patients face every day into our laboratories, focusing investigations on finding solutions that will make a meaningful difference to our patients without delay. Our collaborative efforts are designing more efficient and effective clinical trials while broadening access to these trials for people with ALS.