Genetics: Edited by Nathaniel H. RobinEnzyme replacement therapy for lysosomal storage diseasesLachmann, Robin H.Author Information Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK Correspondence to Robin H. Lachmann, PhD, FRCP, Charles Dent Metabolic Unit, Box 92, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK E-mail: [email protected] Current Opinion in Pediatrics: December 2011 - Volume 23 - Issue 6 - p 588-593 doi: 10.1097/MOP.0b013e32834c20d9 Buy Metrics Abstract Purpose of review Enzyme replacement therapy (ERT) for type 1 Gaucher has been highly successful. ERT is now available for other lysosomal storage disorders (LSDs) but none of these highly expensive treatments has had the same efficacy. This review explores why these newer treatments have failed to live up to expectations and how future products might be made more effective. Recent findings In Gaucher, the target cells for ERT are macrophages, which are efficiently accessed by intravenously injected recombinant enzyme. The target tissues in other LSDs receive much lower doses of enzyme and intravenous ERT does not enter the brain at all. Uptake of recombinant enzyme is via the mannose-6-phosphate receptor (M6PR). Recent work has looked at improving the efficiency of enzyme delivery to tissues by altering both the ligand on the infused enzyme and the expression of the M6PR on cells. For delivery to the central nervous system, intrathecal routes of administration have been explored. Summary Work in tissue culture and in animal models has shown increased efficiency of enzyme delivery and clinical trials of second-generation products and novel delivery systems are now underway. © 2011 Lippincott Williams & Wilkins, Inc.