Hypertension Drugs Unexpectedly Fight Lysosomal Disorders

In studies on patient-derived cells, two FDA-approved hypertension drugs have proven to be effective at ameliorating multiple characteristics of lysosomal storage diseases, conditions in which macromolecules accumulate in lysosomes (acidic degradation compartments) because of deficient activity by misfolded and degraded enzymes (PLoS Biol., DOI: 10.1371/journal.pbio.0060026). The most common of these disorders is Gaucher disease, which can cause spleen enlargement, anemia, brain damage, and other symptoms. The diseases are currently treated by enzyme-replacement therapy, but enzymes must be injected and the treatments are very expensive. Injected enzymes also can't pass the blood-brain barrier and therefore aren't effective against neurological symptoms. Jeffery W. Kelly and coworkers at Scripps Research Institute now have found that the calcium channel blockers diltiazem (which crosses the blood-brain barrier) and verapamil partially restore the folding and function of defective enzymes in cells derived from patients with lysosomal diseases. The researchers believe the drugs work by upregulating chaperone proteins that help deficient enzymes fold properly.