UMass team discover new molecules that may cure rare disease

By David Barnstone


Biochemists and a doctoral candidate at the University of Massachusetts have discovered two new molecules that may lead the way to improved treatment of a rare human disease.

Associate Professor of Biochemistry Scott Garman and alumnus Nathaniel Clark are part of a research team that have discovered two molecules through x-ray crystallography that are promising as ingredients for the first ever drug treatment for the rare metabolic disorder Schindler (or Kanzaki) disease.

Schindler/Kanzaki disease is a disorder, part of a family of 50 diseases that collectively affect between 7,000 and 8,000 births per year, according to a UMass press release. The disorder is characterized by the dysfunction of a gene that codes for a particular enzyme involved in removing toxic waste from cells.

People who have the disease often experience seizures and muscle weakness, the release reported. There is currently no cure and very few options for treatment.

Nathaniel Clark, a doctoral candidate at UMass, and his adviser, Scott Garman, show how two molecules help stabilize these low functioning enzymes produced by people with Schindler/Kanzaki disease as well as for the first time how the enzymes bind to one another in their paper.

“As the culmination of Nate Clark’s Ph.D. thesis, it’s a great achievement for him,” Garman said in the press release. “We were the first to discover the enzyme’s structure in 2009, and now we’ve discovered the small molecules that bind and stabilize that enzyme.”

Garman said their findings “can be applied to the whole family of lysosomal disorders,” according to the press release.

Clark and Garman collaborated on this project with other researchers at UMass and from Oxford University in the U.K. Their work has been published in the Proceedings of the National Academies of Sciences.

David Barnstone can be reached at [email protected]