Richard Vachet, chemistry, received a four-year, $1.2 million grant from the National Institutes of Health to continue his group’s study of the aggregation by βeta-2-microglobulin (β2m), the protein that forms amyloid fibril deposits in the joints of patients with kidney disease who are undergoing dialysis.
Vachet and colleagues will develop new measurement tools using mass spectrometry to understand the molecular details associated with β2m amyloid formation and will apply this understanding to study potential drugs that could stop this process.
He says, “The hope is that our studies will eventually lead to drug treatments against drug-related amyloidosis (DRA) a condition that currently has no treatment except a kidney transplant,” adding that the polymerization of normally soluble proteins into insoluble amyloid fibrils is implicated in more than 20 human diseases, including Alzheimer’s, Parkinson’s, type II diabetes and DRA.
The molecular steps involved in amyloid formation remain unclear, however, so current treatments for these diseases are often ineffective. Vachet says new techniques developed in his lab could soon change this. Using special chemical reagents and mass spectrometry, he and colleagues can now study molecules that are precursors to the insoluble amyloid fibrils, opening up the possibility of designing small molecule drugs to prevent the formation of these precursors and preventing protein aggregation altogether.
He says, “While preventing β2m amyloid formation is important for the half-million people in the United States who suffer from DRA, the new methods we’re developing have the potential to probe the precursor molecules associated with other amyloid diseases, such as Alzheimer’s and Parkinson’s.”
Armed with such information, scientists may one day be able to rationally design therapeutic strategies against these debilitating amyloid diseases, Vachet said.