Current and emerging therapies for the lysosomal storage disorders.
Targeted treatments for the lysosomal storage disorders (LSDs), in the form of enzyme replacement and/or substrate depletion, have been shown to be relatively safe and effective in reversing core disease features in selected clinical subtypes (including Gaucher disease types I and III, Fabry disease and the Hurler-Scheie syndrome). These approaches have expanded the therapeutic options available to patients with rare genetic disorders, beyond palliative measures (such as liver or kidney transplantation for end-organ failure) and cellular replacement through bone marrow transplantation. Present efforts are focused on the development of novel strategies, including chaperone-mediated enzyme enhancement and genetically engineered stem cell therapy. In the coming decades, a broadening therapeutic horizon for patients with inborn errors of metabolism is anticipated, and the growing experience in the management of patients with LSDs will serve as an instructive model. Among the many challenges will be determination of the extent to which these therapies have modified the course of disease beyond merely extending the age of survival, but also enabling a meaningful patient quality of life, and the minimisation of current resource use. The projected lifetime acquisition costs of newly introduced therapeutic options also raises several issues, related to equitable access and the large opportunity costs for other therapeutic areas, that will need to be addressed by healthcare policy makers and third-party payers.
Pastores
Gregory M
GM
Division of Neurogenetics, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA. gregory.pastores@med.nyu.edu
Barnett
Natalie L
NL
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000235:genetics* / Q000378:metabolism / Q000601:surgery
D015507:Drugs, Investigational