Therapeutic approaches for LSDs

A formal evaluation of therapy efficacy in lysosomal diseases is difficult due to the marked variability of clinical phenotypes. Notwithstanding, remarkable advances have been made in the last decade for the treatment of lysosomal storage disorders. The particular characteristics of LSDs make them excellent candidates for the development of therapeutic strategies.

These approaches can be divided into three main types:
a) Approaches aimed at increasing the amount of enzyme available
• Enzyme replacement (ERT)
• Enzyme enhancement (EET)
• Bone marrow or HSC transplantation
• Gene therapy
b) Approaches based on the reduction of the stored material
• Substrate reduction (SR)
c) Approaches for the treatment of secondary effects (will not be dealt by the EUCLYD consortium).

Enzyme replacement and enhancement therapies have been developed to treat these disorders, albeit with variable results. New treatment strategies are being considered for patients with LSDs including gene therapy, substrate reduction therapy and chaperone therapy. These new developments must be accompanied by precise knowledge of the natural history of these disorders which is essential to evaluate the long-term therapy efficacy. The identification and development of animal models recapitulating the clinical course of LSDs are crucial in evaluating therapeutic strategies.

Individuals with lysosomal disorders will greatly benefit from continual refinement and optimization of the current therapy, as well as from the development of new treatment modalities that offer improvements in efficacy, cost, safety and availability.