Single molecule that targets both amyloid and tau could treat Alzheimer's

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NeuroPhage's GAIM molecule disrupts misfolded protein assemblies and clears them from cells.

The Alzheimer's research field has been marked by one failure after another in pursuit of effective treatments, but Cambridge, MA-based NeuroPhage Pharmaceuticals thinks it can tackle the devastating disease with a novel approach.

In a preclinical study published on April 22 in the Journal of Molecular Biology, the company describes a new molecule it's developing based on a platform it calls a general amyloid interaction motif, or GAIM. GAIM works by recognizing and seeking out a characteristic common to many toxic misfolded proteins and targeting key stages of misfolded protein assembly to convert toxic assemblies into nontoxic ones, blocking the spread of misfolded proteins within cells.

When tested in vitro, NeuroPhage researchers found that the GAIM molecule can prevent the formation of new toxic protein aggregates and clear existing plaques and tangles.

Misfolded, toxic proteins are known to occur in various organs of the body--including the brain, heart and liver--and have been implicated in a number of diseases, such as Alzheimer's, Huntington's and amyloidosis. NeuroPhage believes its technology can be used on an array of therapeutic targets so that a number of neurodegenerative diseases associated with misfolded proteins could be addressed with a single drug candidate.

NeuroPhage is focusing first on Alzheimer's disease, which has proved an elusive target with drug developers in the dark about the role of amyloid-β and tau proteins in the pathogenesis of the disease.

"This is something that can target multiple kinds of misfolded protein," Dr. Richard Fisher, NeuroPhage's chief scientific officer, told FierceBiotechResearch in an interview. "In the case of Alzheimer's, it's very important to target more than one kind of protein because no one knows which of the two, or if both of these, drive the progression of the disease."

Fisher said one of the reasons so many Alzheimer's drugs have failed in trials is because they were targeting the wrong form of amyloid β instead of binding to preexisting plaque.

"None of the drugs that have been tested and failed can target more than one type of misfolded protein," Fisher said.

NeuroPhage closed a $17 million venture round in March to back its GAIM platform, and the company hopes to begin clinical trials at the end of 2015.

- read the press release
- see the study abstract