Chaperone drugs show promising results

Amicus Therapeutics has reported positive results from Phase I trials of two different chaperone drugs - so called because they bind to proteins and help them fold up into the correct structure and so prevent disease. The drugs are being tested as possible treatments for Gaucher and Fabry diseases. Misfolding proteins have been implicated in many diseases, including Gaucher and Fabry - two examples of lysosomal storage diseases, which affect 1 in 5000 people, typically children. The two diseases are currently effectively treated by enzyme replacement therapy. However, children with Fabry's often die prematurely of complications from heart disease, renal failure, or stroke, according to US National Institute of Neurological Disorders and Stroke. Amicus' new approach to therapy could provide a valuable alternative to those suffering from these rare disorders. Plicera (isofagomine) has recently completed Phase I clinical trials. The drug is designed to stabilise GCase, the protein deficient in Gaucher disease. Once stabilised, GCase can move to the lysosome part of a cell and break down another protein called glucocerebroside. Increased levels of this protein is believed to cause the various symptoms of Gaucher disease. Amicus has also recently initiated a Phase II trial for Amigal (migalastat). This drug works in a similar was to Plicera, only this time stabilising an enzyme called alpha- galactosidase (alpha-GAL). Data from an earlier Phase I clinical trial was reported this week, with promising results. In both sets of trials, the stabilised enzyme was found in higher concentrations that without treatment and no serious side effects were seen.