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Scripps scientists find calcium channel blockers help normalize lysosomal storage disease cells
Date:2/4/2008

The study was published online February 5 in the February 2008 edition (Volume 6, Issue 2) of the journal PLoS Biology.

The research team found that the hypertension drugs diltiazem and verapamil increased the overall function of mutant lysosomal enzymes associated with the conditions Gaucher disease, -mannosidosis, and type IIIA mucopolysaccharidosis in patient-derived cell lines. The drugs worked by reprogramming the innate protein homeostasis machinery of the cell to repair the mutant enzymes. These findings may be especially significant for patients with lysosomal storage diseases affecting the brain, for which there is currently no effective treatment.

"Our study shows that these two widely prescribed calcium channel blockers restore partial enzyme homeostasis in cell lines derived from patients suffering from several lysosomal storage diseases," said team leader Jeffery Kelly, who is Lita Annenberg Hazen Professor of Chemistry, Dean of Graduate and Postgraduate Studies, and member of the Skaggs Institute of Chemical Biology at Scripps Research. "The extent of restoration of mutant enzyme function is thought by many to be sufficient to ameliorate these diseases, opening the door to a new and potentially effective therapy for these patients, especially those suffering from neuropathic lysosomal storage diseases. As with all new therapeutic strategies, safety and efficacy must be demonstrated in humans."

The fact that both diltiazem and verapamil are approved by the Food and Drug Administration for the treatment of cardiovascular disease may pave the way for their use in the treatment of lysosomal storage diseases, once further testing is completed.

Lysosomal storage diseases result from deficient enzyme activity that leads to an accumulation of molecules that the enzymes break down in the lysosomes, organelles or subcellular compartments that normally break down macromolecules utilizing hundreds of degradatory enzymes. I
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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