Substrate Reduction Therapy

Oral substrate reduction therapy (SRT) involves attenuation of the rate of synthesis to achieve a balance with reduced endogenous glucocerebrosidase.

A pivotal trial of SRT was carried out in 28 adult patients (from four centers: Cambridge, UK; Amsterdam; Prague; and Jerusalem) naive to enzyme therapy, with mild to moderate type I Gaucher disease, who were unable or unwilling to receive enzyme treatment. There was significant reduction in spleen and liver, although amelioration of anemia and thrombocytopenia lagged behind. There were side effects, including diarrhea, abdominal pains, weight loss, tremor, and peripheral neuropathy, which were reversible with dose reduction or withdrawal.[15] A low-dose trial showed dose dependency for clinical improvement but no reduction in severity or frequency of side effects. Finally, using SRT as a maintenance regimen (i.e., switching from ERT or in combination with ERT), at 6 months, there were no clinically significant differences among groups.

SRT, commercially available as Zavesca™ (Actelion Pharmaceuticals, Allschwil, Switzerland; Teva Pharmaceuticals Israel, Netanya, Israel), has received European, Israeli, and American approval for patients with mild to moderate Gaucher disease, for whom ERT is unsuitable or not a therapeutic option, respectively. Because it is a small molecule capable of crossing the blood-brain barrier, this drug may potentially improve neurological features in Gaucher disease and other lysosomal storage disorders, in whom benefits may outweigh risks and discomforts of the drug in its current formulation.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook

Post a comment