The two major approaches to (non-neurological manifestations of) Gaucher disease are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). There are also a large number of adjunctive therapies that are used to manage the clinical manifestations of the disease and end-organ damage.
Enzyme replacement therapy (ERT)
Enzyme replacement therapy aims to provide the correct amount of enzyme to allow GL-1 to be removed from the cell. This provides the central feature of therapy for Gaucher disease, but does not currently address neurological symptoms associated with types 2 and 3 disease. Pastores G, Weinreb N, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol 2004;41 (suppl 5):4-14
When Gaucher Disease presents during childhood or adolescence, this can be associated with more-severe disease. ERT treatment is available for children suffering from Gaucher disease. Kallish S, Kaplan P. A disease severity scoring system for children with type 1 Gaucher disease. Eur J Pediatr. 2013 Jan;172(1):39-43.
Pregnancy in Gaucher disease exacerbates disease manifestations, and ideally therapeutic goals should be achieved before considering a pregnancy. Cox TM, Aerts JM, Belmatoug N, Cappellini MD, vom Dahl S, Goldblatt J, Grabowski GA, Hollak CE, Hwu P, Maas M, Martins AM, Mistry PK, Pastores GM, Tylki-Szymanska A, Yee J, Weinreb N. Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. J Inherit Metab Dis. 2008 Jun;31(3):319-36 The experiences with ERT in pregnancy may vary per treatment product. To know whether a product is indicated for use during pregnancy, please refer to the Summary of Product Characteristics (SmPC).
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Substrate reduction therapy (SRT)
Substrate reduction therapy (SRT) is a possible available treatment alternative to ERT, in adults with Gaucher disease type 1. This therapy aims to decrease the rate of synthesis of glucosylceramide (the substrate), resulting in decreased further accumulation in the lysosomes. Aerts JM, Hollak CE, Boot RG, Groener JE, Maas M. Substrate reduction therapy of glycosphingolipid storage disorders. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):449-56. In addition, even though Gaucher patients are enzyme deficient they may still be able to reduce previously stored glucosylceramide. Shayman JA. The design and clinical development of inhibitors of glycosphingolipid synthesis: will invention be the mother of necessity? Trans Am Clin Climatol Assoc. 2013;124:46-60.
Many patients with Gaucher disease will require further ongoing treatment to manage the individuals particular manifestations. These could include: Pastores G, Weinreb N, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol 2004;41 (suppl 5):4-14
- pain relief
- physical therapy for skeletal complications
- bisphosphonates for osteopenia
- vasodilator therapy for pulmonary hypertension.
Gene therapy and small molecule pharmacological chaperone therapy (enzyme enhancement therapy) are being investigated as potential approaches in developing the optimal management of Gaucher disease in the future. Mistry PK, Cappellini M, Lukina E, et al. Consensus Conference: a reappraisal of Gaucher disease – diagnosis and disease management algorithms. Am J Hematol 2011;86(1):110-115.