Enzyme Replacement or Substrate Reduction? A Review of Gaucher Disease Treatment Options

Abstract

Background Gaucher disease is a rare lysosomal storage disease resulting from a deficiency or reduced activity in the acid β-glucocosidase enzyme. Only 1 treatment option was available for 15 years, but several new treatment options have come to market since 2003. Objective The article will detail the pathophysiology and review current therapies in the literature for all 3 major clinical types of Gaucher disease, with a focus on considerations for selecting therapy in type 1 disease. Methods Extracted and summarized applicable studies and reviews from Cochrane Review, ClinicalTrials.gov , CINAHL, IPA, and PubMed. Results Enzyme replacement therapy is preferred for the management of Gaucher disease. Current literature does not favor any enzyme replacement product over another. However, velaglucerase alfa and taliglucerase alfa theoretically have a lower risk of immunogenicity reactions compared with imiglucerase. Alternative treatments for type 1 disease include substrate reduction therapy; however, these treatments require evaluation of patient-specific variables (eg, genotype evaluation, renal function) and consideration of adverse effect and dosing profiles. Evaluation of current literature found no substrate reduction therapy is preferred over another. There are no approved therapies for type 2 and type 3 disease, but enzyme replacement therapy may be used with limited efficacy for symptom management. Conclusion Enzyme replacement therapy is preferred for treating type 1 Gaucher disease and substrate replacement therapy may be considered in patients who do not tolerate or cannot receive enzyme replacement therapy.