Toward a less expensive, more convenient treatment of Gaucher's disease

Prospects for eventual development of a less costly and more convenient treatment for Gaucher's disease have brightened with new research findings reported in the May issue of ACS Chemical Biology.

The existing treatment costs up to $750,000 annually for a single patient, continues for life, and must be given intravenously rather than by mouth. An oral treatment based on the new research could cut those costs by 100-fold.

Gaucher's (go-SHAYZ) disease is rare, but ranks as the most common lysosomal storage disorder and genetic disorder affecting Jewish people of Eastern European ancestry. Individuals with Gaucher's disease, which can be fatal, produce a defective form of GC, a critical enzyme that breaks down a fatty substance called glucosylceramide.

In the new report, scientists have confirmed experiments they reported initially in 2002 that "chemical chaperones" can partially correct the genetic defect responsible for most cases of Gaucher's disease. Like aspirin, penicillin and most other existing drugs, chemical chaperones are small molecules -- natural and synthetic substances with a low molecular weight.

Using patient-derived cell lines, researchers have extended those earlier studies to provide new insights into the defect and how chaperones correct it. The defect involves protein misfolding and prevents a key enzyme, glucocerebrosidase (GC), from reaching the location in cells where it normally functions. Jeffrey W. Kelly, Ph.D., of the Scripps Research Institute (TSRI) in La Jolla, Calif., headed the research team.

"Gaucher's disease patients can now be treated with enzyme replacement therapy," Kelly explained. "The hope is that this current strategy could be replaced with a small molecule chemical chaperone therapy wherein the cost would be reduced by at least 100-fold." Although enzyme replacement therapy is highly effective in treating Gaucher's disease, treatment often costs $100,000-$750,000 annually for each patient. With abnormal glucosylceramide, Gaucher's patients accumulate GC in the spleen, liver, lungs and bone marrow. As those cells become engorged with the enzyme, patients experience a range of health problems including anemia, bone fractures and sometimes lung and brain disorders. Kelly said researchers are now trying to identify an optimal small molecule that could be suitable for use as a chemical chaperone in clinical trials.

The research team included Anu R. Sawkar, Ph.D., and William E. Balch, Ph.D., of TSRI; Martina Schmitz, Ph.D., and Klaus-Peter Zimmer, Ph.D., of Westfälische Wilhelms-Universität in Münster, Germany; and David Reczek, Ph.D., and Tim Edmunds, Ph.D., of Genzyme in Cambridge, Massachusetts.


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The online version of the research paper cited above was published May 23 on the journal's Web site. Journalists can arrange access to this site or request a copy of the paper by sending an e-mail to [email protected] or calling the contact person for this release.

Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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