Rejected Drug Should Remain a Contender for Neurodegenerative Conditions

Scientists show a renewed interest in latrepirdine as a treatment for a number of neurodegenerative disorders after experiments with the drug exhibited improved memory function in animal models.

Latrepirdine is a drug that showed efficacy in treating some of the earliest animal models of Alzheimer’s disease in Russia the 1990s. The drug was rejected as a possible treatment option, however, after it failed to show improvement in people with the disease in Phase III trials conducted in the United States.

“Despite the failure to replicate the positive Russian trial results in United States patients, we found unexpected evidence that latrepirdine had potential for a number of neurodegenerative disorders,” said Sam Gandy, MD, PhD, professor of psychiatry and director of the Mount Sinai Alzheimer’s Disease Research Center, and lead researcher of 2 new studies analyzing the function of latrepirdine. “Our study shows that the compound prevents neurodegeneration in multiple ways and should remain a contender for battling these devastating diseases.”

Investigators determined that latrepiridine activated autophagy in mice, yeast, and mammal cells. From the results of 2 new studies published in Molecular Psychiatry, scientists noticed in mice bred to develop early Alzheimer's disease that latrepirdine activated autophagy of alpha-synuclein, a protein believed to cause neurodegeneration. The second study revealed that latrepirdine protects yeast cells from the toxicity of alpha-synuclein.

The authors of the studies believe that based on their new findings, latrepirdine may be effective in treating or preventing disorders that rely on the accumulation of alpha-synuclein, such as Parkinson’s disease, Lewy body dementia, and REM sleep disorder. The scientists attributed their previous failures with latrepirdine to not thoroughly understanding the drug’s mechanism of action. The mTOR signaling pathway, which regulates autophagy, could represent a suitable target for intervention in neurodegenerative diseases, the authors noted.