Table 1.

Therapeutic approaches for lysosomal storage disorders (LSDs).

Therapeutic option

Candidate diseases

Bone marrow or umbilical cord blood transplantation Enzyme replacement therapy Substrate reduction therapy Substrate depletion therapy Substrate modulation (optimization) therapy* Chaperone-mediated enzyme enhancement* Premature stop codon read through* Gene therapy* Antisense splicing modulation therapy*

Hurler (MPS IH), Maroteaux-Lamy (MPS VI), globoid-cell leukodystrophy (Krabbe disease), metachromatic leukodystrophy (MLD), α-mannosidosis Gaucher disease (GD), Fabry disease (FD), Hurler—Scheie (MPS I), Hunter (MPS II) syndrome, Maroteaux—Lamy (MPS VI), Pompe disease (GSD II). Investigational: recombinant acid and sphingomyelinase (Niemann—Pick B) Approved for GD, Niemann—Pick type C (miglustat); Investigational for FD, late-onset GM2-gangliosidosis (LOTS), Sandhoff disease. Investigational drugs: eliglustat (GD) and genistein (MPS) Cystinosis MPS disorders GD, FD and GSD II MPS I Almost all LSDs, mainly mouse models, except for GD wherein early human trials were done Niemann—Pick C

^*Approaches for which there is no agent which has gained regulatory approval.