A-synuclein drug therapy in the pipeline for Alzheimer’s, Parkinson’s

A potential therapy targeting the misfolded proteins in neurodegenerative disease including Alzheimer's, Parkinson’s and Huntington’s disease is edging closer to human trials, NeuroPhage Pharmaceuticals announced April 22.

The company, based in Cambridge, Mass., is working to address a range of pathologies from tau fibrillary tangles to Lewy bodies and beta-amyloid plaque in a single therapeutic dose that is intended to not only treat existing pathology but also prevent future development. It is being called NPT088. The clinical investigation was published online today in the Journal of Molecular Biology.

The drug is based on NeuroPhage’s GAIM platform of development, which stands for general amyloid interaction motif. "The research published today describes GAIM, NeuroPhage's unique approach to treat diseases characterized by misfolded proteins. GAIM has the potential to provide a more robust response than previous therapies because it enables the simultaneous targeting of multiple pathologies within a single disease," said Richard Fisher, MD, Chief Scientific Officer at NeuroPhage.

“Symptoms of neurodegenerative diseases often appear well after the troublesome aggregates have begun to accumulate in the brain. By then, therapies that only target newly forming aggregates are likely to only slow the progression of the disease and are believed to be too late once the aggregates are formed," said Gregory A. Petsko, MD, professor of neurology at Weill Cornell Medical College in New York City. "Therapies based on GAIM would represent a completely new paradigm in the treatment of many neurodegenerative diseases with their potential to ameliorate existing symptoms and prevent disease progression. The hope is this will eventually lead to a real treatment for Alzheimer's disease, but for now, the science behind it is quite compelling."

The scientists used nuclear magnetic resonance spectroscopy and X-ray fiber diffraction to test their compound, which is conjugated with a human antibody. Human studies could begin as early as fourth quarter 2015.

"With recent advances in imaging agents for beta-amyloid and tau in Alzheimer's disease, we believe we should be able to demonstrate clinical proof of mechanism in a Phase 1b study with NPT088," said Jonathan Solomon, CEO at NeuroPhage. "If successful, we would then have the opportunity to pursue many therapeutic options in several neurodegenerative diseases of protein aggregation."