Amylyx will receive $1.85 million for the trial of AMX0035, which consists of an oral formulation of sodium phenylbutyrate (PB) and tauroursodeoxycholic-acid (TUDCA).
PB activates genes responsible for protecting brain cells from toxic unfolded proteins. The U.S. Food and Drug Administration has approved the compound for urea-cycle disorders, metabolic dysfunctions that make it hard for the body to break down proteins. TUDCA is an acid that the body produces in small quantities to prevent cell energy loss.
In preclinical-trial studies, the combination therapy was shown to protect brain cells from inflammation and oxidation. Oxidation is the process by which the body converts food into energy. It can be harmful when it generates free radicals, which can damage the body.
“Combination therapies hold great potential to slow the progression of Alzheimer’s,” Dr. Howard Fillit, the the drug discovery foundation’s chief science officer, said in a press release. “The innovation of Amylyx’s combination therapy is that it targets multiple causes of brain cell loss, and the two drugs given in tandem create additional protective effects. The foundation “was an early supporter of innovative targets for Alzheimer’s, and we believe combination therapies are a critical next step in finding effective treatments for the disease.”
The trial is expected to begin in the first half of 2018. It will involve about 50 people with mild cognitive impairment or mild-to-moderate Alzheimer’s. The main objective will be to evaluate the drug’s ability to slow or stop brain cell death.
“Through a combination approach targeting two different and independent pathways, AMX0035 is designed to benefit both neurodegeneration and neuroinflammation, key drivers of Alzheimer’s and ALS,” said Kent Leslie, Amylyx’s chief scientific officer. “The biomarker-focused trial design will assist in translating the promising preclinical effects observed in models of Alzheimer’s to an improved understanding of the potential of AMX0035 to help individuals living with this disease.”
The grant is the first award under the Alzheimer’s Combination Therapy Opportunities initiative. The Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation started the program in 2015 to support clinical trials testing combination therapies. A special focus of the program is repurposed drugs, or those already approved for other diseases that might be useful in new combination therapies.