Novel Therapy Efficacious for Alzheimer's, Parkinson's Disease
NPT088, from NeuroPhage Pharmaceuticals, targets proteins related to amyloid beta, tau.
WASHINGTON — Results of a study in mice presented at the Alzheimer's Association International Conference 2015 indicate that NPT088, a first-in-class therapeutic agent for Alzheimer's disease, targets misfolded proteins generically, including aggregates of amyloid beta and tau.
“NPT088 effectively treats brain pathologies in mouse models of both Alzheimer's and Parkinson's disease, which we believe is unique for a drug candidate,” study investigator Richard Fisher, PhD, of NeuroPhage Pharmaceuticals, Cambridge, Mass., said in a statement.
For the study, Fisher and colleagues tested NPT088, a therapy that includes a general amyloid interaction motif (GAIM), in a mouse model. According to investigators, the GAIM molecule “blocks misfolded proteins from aggregating, protects cells from protein aggregate toxicity, and targets multiple types of aggregated proteins, including amyloid beta, tau, and alpha-synuclein.”
Researchers found that NPT088 specifically and potently binds amyloid fibers of amyloid beta, tau, and alpha-synuclein, but not monomers or natively aggregated proteins.
They also observed that NPT088 binds amyloid beta oligomers, blocks oligomer-induced cytotoxicity, and prevents amyloid beta and tau aggregation, as well as recognizes brain homogenate amyloid beta aggregates in aged Tg2576 mice.
The therapy also effectively treated Alzheimer's disease and Parkinson's disease in transgenic mice.
In the Tg2576 hAPP model, NPT088 improved cognition, reduced brain amyloid beta (1-42) and amyloid beta plaque, and decreased cerebrospinal fluid (CSF) amyloid beta, while in rTg4510 tau mice, it significantly improved cognition, reduced levels of phosphorylated-tau protein associated with neuropathology and decreased CSF tau.
Researchers added that 1-month exploratory monkey and rat safety studies on NPT088 have been successfully completed, and that the therapy is currently in the final stages of safety testing before the initiation of clinical trials.
“Pending regulatory approval, we plan to begin clinical testing in people with Alzheimer's in early 2016,” Fisher said.
Fisher R, et al. Presentation #O1-05-01. Discovery, Preclinical development, and clinical trial approach for NPT088, a general amyloid interaction motif (GAIM)- immunoglobulin fusion. Presented at: Alzheimer's Association International Conference 2015; July 18-23, 2015; Washington, D.C.