UMass biochemists advance study of enzymes

By Dan Glaun

Researchers at the University of Massachusetts, led by biochemistry and microbiology professor Scott Garman, have published a study of molecular bonding to enzymes which could advance the treatment of Fabry disease, as well as other diseases like Tay-Sachs, Alzheimer’s and Parkinson’s.

The study, recently published in the journal “Chemistry & Biology,” analyzed a molecular therapy of Fabry disease and determined a more efficient way of delivering the treatment.

Fabry disease is a genetic disorder which affects between one in 40,000 and one in 60,000 men with a much lower incidence in women, according to the National Institutes of Health. Symptoms include episodes of pain, red spots on the skin, and hearing loss, as well as potentially fatal complications such as kidney damage, heart attack and stroke.

The research was conducted by Garman and a research team of UMass graduate students Abby Guce, Nat Clark and Jerome Rogich. It received funding from the NIH, the National Science Foundation, the Charles H. Hood Foundation and UMass. The study came together over a period of years as the UMass researchers conducted experiments and analyzed the results.

The study is an addition to the body of research produced by UMass scholars and scientists, which has earned the university international recognition. The Times Higher Education, a London-based magazine focused on upper-level education news, ranked UMass the 19th most highly regarded university in the world in its 2011 World Reputation Rankings.

Garman’s research team studied the binding of molecules to the alpha-galactosidase protein, which is defective in Fabry patients. A treatment of the disease called pharmacological chaperone therapy, currently in clinical trials, normalizes the affected enzyme by binding small molecules to the protein.

“Our work looked at some of the basic biochemistry underlying pharmacological chaperone therapy for Fabry disease,” wrote Garman in an email.

“We studied two chaperones, one that binds tightly and one that binds loosely. Our results showed that the difference between the tight binder and the loose binder is due to a single atomic interaction,” wrote Garman. “This is an important result for understanding how to design better pharmacological chaperones. Tight binding compounds are better candidates for the pharmaceutical industry, because less compound is needed to get the same effect.”

While Fabry disease was the focus of the research, the insights made by Garman’s team could have implications for a variety of diseases caused by defective proteins, including Alzheimer’s and Parkinson’s.

Dan Glaun can be reached at [email protected].