Gaucher disease patients have a mutation in the GBA gene that provides instructions to build the enzyme beta-glucocerebrosidase (GCase). GCase breaks down the fatty substance glucocerebroside. The mutation causes either a dysfunction or deficiency of the enzyme, which leads to an accumulation of glucocerebroside in different tissues and organs such as the spleen, liver, bone marrow, and lungs.
Enzyme replacement therapy
Enzyme replacement therapy is intended to replace the defective GCase enzyme with a functional one. The functional enzyme is delivered into the bloodstream through a vein. This process takes between one and two hours and has to be repeated every two weeks.
Because the enzymes cannot cross the blood-brain barrier, enzyme replacement therapy is only effective for non-neuronopathic forms of Gaucher disease and cannot prevent the progression of brain damage that occurs in Gaucher disease types 2 and 3.
Cerezyme (imiglucerase) by Sanofi Genzyme, VPRIV by Shire, and Elelyso (taliglucerase alfa) by Pfizer are U.S. Food and Drug Administration (FDA)-approved enzyme replacement therapies for Gaucher disease.
Substrate reduction therapy
Substrate reduction therapy inhibits the synthesis of glucocerebroside, the fatty substance that is broken down by GCase. Consequently, there are fewer waste products to be removed by GCase. Substrate reduction therapy can be combined with enzyme replacement therapy. The treatment is less invasive than enzyme replacement therapy because it is taken orally.
Cerdelga (eliglustat) by Sanofi Genzyme is used as first-line treatment for patients with type 1 Gaucher disease. Zavesca (miglustat) by Actelion Pharmaceuticals is used for the treatment of patients with mild to moderate type 1 Gaucher disease who cannot be treated with enzyme replacement therapy.