Other Potential Therapies

Metabolic Bypass Therapy

Metabolic bypass therapy is another biochemical approach that makes use of special chemicals called activators to increase the synthesis or activity of alternative lysosomal enzymes to make them capable of degrading larger amounts of a substrate like sphingomyelin than normal. If one could increase the activity of an enzyme other than Acid Sphingomyelinase (ASM) to degrade sphingomyelin, then it could partially compensate for the absence of ASM and “by-pass” the cell’s need for ASM. This approach is still theoretical, but researchers are currently looking for activators and appropriate “by-pass” enzymes.

Substrate Deprivation/Substrate Inhibition

Substrate deprivation (also called substrate synthesis inhibition, substrate reduction, substrate balancing) is a biochemical approach that makes use of novel chemicals called inhibitors that decrease the production of the molecule that typically accumulates to high levels in persons with lysosomal storage diseases. For example, children with Niemann-Pick Type A accumulate high levels of sphingomyelin in brain cells and it is this accumulation which causes the brain cells to die. If one could decrease the synthesis of sphingomyelin, the substrate for the missing enzyme, then one would presumably decrease cell death and moderate the course of the disease. The inhibitor Zavesca ® (miglustat) is currently in clinical trials for individuals affected with Niemann-Pick Type C.