Recent advances in treatment approaches to Gaucher disease.

Gaucher disease is inherited as an autosomal recessive disorder. The absence of β-glucocerebrosidase whose purpose is to cleave the glucose from ceramide results in accumulation of glucocerebroside; storage of this glycolipid results in Gaucher disease. There is tremendous clinical heterogeneity: prediction of onset of symptoms (if at all), which organs will be affected, and the degree of severity of the signs and symptoms are areas of current research. Lysosomal storage diseases may be treatable by enzyme replacement therapy. Enzyme replacement for Gaucher disease has been attempted intermittently since the middle 1970s but was not successful until removal of sugars to expose the inner mannose residues allowed the targeting of the enzyme to macrophages via mannose receptors. The use of the recombinant imiglucerase (Cerezyme™) as intravenous therapy has been safe and effective for the visceral symptoms and signs of Gaucher disease in more than 5000 patients world-wide for more than 18 years. Nonetheless, beyond enzymes not being able to traverse the blood-brain barrer, dependence on a single modality is problematic since not all patients are responders, some develop adverse events, and supply may not be forthcoming for non-medical reasons. Thus, the availability of new enzymatic preparations, velaglucerase alfa (VPRIV™) and taliglucerase alfa (UPLYSO™), as well as alternative modalities such as substrate reduction and pharmacological chaperones, are important additions to the management portfolio of this disease.