Therapy for Neuropathic Lysosomal Storage Diseases

Lysosomal storage diseases (LSDs) have phenotypic manifestations in multiple organ systems, most notably the central nervous system (CNS). LSDs can be classified broadly as sphingolipidosis (SL), mucopolysaccharidoses (MPS), mucolipidosis (ML), multiple enzyme deficiencies (MEDs), oligosaccharidoses (OS), and neuronal ceroid lipofuscinosis (NCF). Enzyme replacement therapy has shown positive outcomes in multiple diseases such as Fabry disease, Gaucher’s disease. Nanoparticle envelopes and liposomes are technological advances that stabilize recombinant enzymes, increase their half-life in the systemic circulation, and enhance their therapeutic effects. Many treatments for LSDs have completed clinical trials and received FDA approval. Despite the success of ERT in ameliorating non-CNS manifestations of LSDs, CNS manifestations are resistant to ERT, primarily because the BBB blocks the delivery of the replacement enzyme to the CNS. Using gene therapy delivered by CED of viral or nanoparticle vectors is also an area of research interest. Better treatments are required for the CNS involvement that accompanies many LSDs and often results in severe morbidity and early mortality.