Targeting Stress Granules: Harnessing Biology to Develop ALS Therapies

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Aquinnah Pharmaceuticals, in partnership with researchers at Boston University, are targeting stress granules to design new therapies for amyotrophic lateral sclerosis (ALS). The goal is to advance promising new drug leads aimed at providing disease-modifying treatments for patients that will slow the clinical progression of this devastating disease.

One of the cornerstones of The ALS Association’s global research program is to fund milestone-driven projects to push research efforts more rapidly toward effective treatments and cures. The Association successfully accomplishes this is through fostering partnerships between academic laboratories and industry, and then funding them through The Association’s TREAT ALS™ Drug Development Contract program grants.

One great example of this type of collaboration is a partnership between Dr. Ben Wolozin, Professor of Pharmacology and Neurology at Boston University School of Medicine and Dr. Glenn Larsen, CEO of Aquinnah Pharmaceuticals based out of Cambridge, Mass. Dr. Wolozin also serves as Aquinnah Pharmaceutical’s Chief Scientific Officer.

The focus of their research is stress granules, which are clumps of RNA and protein that accumulate in a cell when it experiences stress. This accumulation allows space for specialized RNA-binding proteins that are designed to clean up the cell. Once the cell is cleaned up, the accumulated RNA and protein disperse out of the stress granule and the cell goes back to its normal function.

Research has shown that when stress granules remain in the cell for a long period of time, it can potentially trigger other problems in the cell, ultimately leading to neurodegeneration. Prolonged stress granules may occur based on a number of factors such as genetic mutations or exposure to environmental toxins.

Importantly, researchers have found that some people living with ALS have cells that are chronically stressed and contain prolonged stress granules, demonstrating that stress granules play a role in ALS.

The goal of Aquinnah Pharmaceuticals is to find a way to harness the body’s biology to break apart and disperse harmful stress granules to ultimately develop disease-modifying therapies for ALS. They began by screening for compounds that convert cells containing harmful stress granules back to normal.

Since then, they have identified several effective stress granule inhibitors. Further work was carried out to modify the compounds so that they can be taken orally and penetrate the brain to target the stress granules.

Currently, efficacy testing is ongoing, and Drs. Larsen and Wolozin expect the company to proceed through the rest of the preclinical phases in the next two to three years. At that point, they will file with the FDA to begin clinical trials.

“It is very exciting to see how quickly this has moved,” said ALS Association Chief Scientist Lucie Bruijn, Ph.D., M.B.A. “We are very encouraged that this could move forward to something meaningful soon.”

In response, Dr. Wolozin stated, “What The ALS Association does enables research to happen and enables the first steps in drug discovery because this area is risky, underfunded and essential to generate the preliminary data required leading up to FDA approval. Funding from The Association largely enables those types of feasibility studies, and so on behalf of Aquinnah and as an academic, I want to thank The ALS Association for all you are doing.”

For more information on the targeting of stress granules, watch Drs. Larsen and Wolozin's recorded webinar, "New Therapeutic Approaches for ALS Based on RNA Binding Proteins," here or read a summary of the webinar here.

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