R.O. Brady

Following the unprecedented success of enzyme replacement therapy (ERT) in patients with Type 1 (non-neuronopathic) Gaucher disease, this therapeutic approach has been applied to a number of other hereditary metabolic storage disorders of humans. I shall discuss the responses to ERT in patients with Fabry disease, Hurler disease, Maroteaux-Lamy disease and Pompe disease. Because impairment of the central nervous system does not improve with ERT alone, additional therapeutic modalities have been initiated to treat patients with brain involvement. Substrate reduction therapy (SRT) has been examined in patients with late-onset Tay-Sachs disease and in patients with Type C Niemann-Pick disease. SRT combined with ERT is currently being evaluated in patients with Type 3 (chronic-neuronopathic) Gaucher disease. Another potential approach is the use of molecular chaperones to augment residual catalytic activity of mutated enzymes. Investigations of this strategy have shown promise in a murine model of juvenile generalized (GM1) gangliosidosis. Other studies provided the foundation for a safety and dose-escalation trial of molecular chaperone therapy in patients with Fabry disease. Finally, the present status of gene editing and gene therapy in metabolic storage diseases will be summarized.

Keywords (Optional): 
Enzyme replacement
substrate reduction