LA JOLLA, CA May 7, 2010 In findings that advance scientists' understanding of a whole class of inherited disorders, a team from The Scripps Research Institute has shed light on a mechanism that enables a potential treatment for Gaucher's disease and other lysosomal storage diseases.
The findings were published in an advance, online edition of the journal Nature Chemical Biology on May 9, 2010.
"This study is likely to motivate clinical trials for the treatment of neuropathic lysosomal storage diseases, including Gaucher's disease, where the current standard of care, enzyme replacement therapy, is ineffective," said team leader Jeffery Kelly, who is chair of the Scripps Research Department of Molecular and Experimental Medicine, Lita Annenberg Hazen Professor of Chemistry, and a member of the Skaggs Institute of Chemical Biology. "The research is especially promising because we enhanced the cellular folding and function of mutated lysosomal enzymes, whose deficient function is linked to lysosomal storage diseases, using two distinct categories of FDA-approved drugs that have been shown to be safe and effective for the treatment of high blood pressure and muscle spasms."
"We wanted to uncover general principles that could be applied to a variety of loss-of-function protein misfolding diseases," added Derrick Sek Tong Ong, a graduate student in the Scripps Research Kellogg School of Science and Technology who was first author of the paper. "This study reveals how we can enhance the capacity of the cellular machinery to fold and traffic a mutant enzyme, so that the protein can function better."
In the new paper, the team revealed how the widely available prescription drugs diltiazem, verapamil, and in some cases dantrolene, acted on cells from patients with Gaucher's disease, increasing calcium levels in a subcellular compartment called the endoplasmic reticuluma convoluted membranous sac within the cell where the foldi
|Contact: Keith McKeown|
Scripps Research Institute