Lysosomal storage diseases (LSDs) often manifest with severe systemic and 
central nervous system (CNS) symptoms. The existing treatment options are 
limited and have no or only modest efficacy against neurological manifestations 
of disease. We demonstrate that recombinant human heat shock protein 70 (HSP70) 
improves the binding of several sphingolipid-degrading enzymes to their 
essential cofactor bis(monoacyl)glycerophosphate in vitro. HSP70 treatment 
reversed lysosomal pathology in primary fibroblasts from 14 patients with eight 
different LSDs. HSP70 penetrated effectively into murine tissues including the 
CNS and inhibited glycosphingolipid accumulation in murine models of Fabry 
disease (Gla(-/-)), Sandhoff disease (Hexb(-/-)), and Niemann-Pick disease type 
C (Npc1(-/-)) and attenuated a wide spectrum of disease-associated neurological 
symptoms in Hexb(-/-) and Npc1(-/-) mice. Oral administration of arimoclomol, a 
small-molecule coinducer of HSPs that is currently in clinical trials for 
Niemann-Pick disease type C (NPC), recapitulated the effects of recombinant 
human HSP70, suggesting that heat shock protein-based therapies merit clinical 
evaluation for treating LSDs.