Amylyx, Project ALS Collaborate on Preclinical Study to Test AMX0035 as Potential ALS Therapy

Project ALS and Amylyx Pharmaceuticals will collaborate on preclinical studies of Amylyx’s lead compound AMX0035 as a potential treatment for patients with amyotrophic lateral sclerosis (ALS).

These studies will complement Amylyx’s recently initiated Phase 2 CENTAUR clinical trial (NCT03127514), which will evaluate AMX0035 in 132 patients.

Since mitochondrial stress and endoplasmic reticulum (ER) stress are understood to be key mediators of both nerve cell death and neuro-inflammatory processes, AMX0035 combines two compounds: tauroursodeoxycholic acid (TUDCA) and sodium phenylbutyrate (PB). Both are dosed in a particular ratio to simultaneously block mitochondrial and ER stress.

The mitochondria is the cell’s powerhourse, producting energy for all cellular processes. The ER is where most protein post-translational modifications take place. These are intricate processes that make a protein fully functional. This combination stems from results of previous studies that suggest TUDCA and PB are effective, safe and tolerable in cellular and animal models of ALS as individual agents.

These studies have also found AMX0035 to prevent nerve cell death and neurotoxic inflammation — both hallmarks of ALS.

The collaborative pre-clinical studies will be conducted at the Project ALS Pre-Clinical Core at Columbia University’s Motor Neuron Center.

“We look forward to evaluating AMX0035 in models of ALS,” Hynek Wichterle and Serge Przedborski, co-directors of the Core, said in a press release. “It is exciting that TUDCA has independently shown promise in both our labs and in studies conducted by the company.”

The Core, created in collaboration with Project ALS, uses a unique, integrated platform to test and validate new therapies, and to discover biomarkers, in experimental models of ALS.

“The collaboration will bring together a promising therapeutic candidate for a devastating disease with leading edge, fundamental neuroscientific research at Columbia,” said Valerie Estess, director of research for New York-based Project ALS. “The studies in this collaboration will provide greater insight into the neurobiological effects of AMX0035, and hopefully optimize its beneficial effects.”

The Phase 2 CENTAUR trial is nowrecruiting patients. For details on eligibility criteria and requirements, contact Carly Doyle at (855) 437-4823 or [email protected].