Enzyme replacement and enhancement therapies for lysosomal diseases.
Although first suggested by de Duve in 1964, enzyme replacement therapy (ERT) for lysosomal storage diseases did not become a reality until the early 1990s when its safety and effectiveness were demonstrated in type 1 Gaucher disease. Today, ERT is a reality for Gaucher disease, Fabry disease and mucopolysaccharidosis type I (MPS I), and clinical trials with recombinant human enzymes are ongoing in Pompe disease, MPS II and MPS VI, and are about to begin in Neimann-Pick B disease. In addition to ERT, enzyme enhancement therapy (EET) offers a novel therapeutic strategy to increase the residual function of mutant proteins. EET employs small molecules as 'pharmacological chaperones' to rescue misfolded and/or unstable mutant enzymes or proteins that have residual function. EET also offers the possibility of treating neurodegenerative lysosomal disorders since these small therapeutic molecules may cross the blood-brain barrier. The current status of ERT and the prospects for EET for lysosomal storage diseases are reviewed.
Desnick
R J
RJ
Department of Human Genetics, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA. rjdesnick@mssm.edu
D057487:Enzyme Therapy; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use*
D011994:Recombinant Proteins