Gene Therapy for Metachromatic Leukodystrophy; MLD

Abstract

Lysosomal storage diseases (LSDs) are a heterogeneous group of diseases caused by genetically determined defects in lysosomal enzymes. Specific molecular mechanisms and disease phenotypes depend on the type of storage material affected. Current treatments for LSDs include enzyme replacement therapy (ERT) and hematopoietic cell transplantation (HCT) from allogeneic healthy individuals. However, those approaches are applicable only to a limited number of LSDs and lack efficacy for some clinical conditions. Hematopoietic stem cell gene therapy (HSC-GT) incorporating lentiviral vectors has shown strong clinical efficacy when administered to patients with metachromatic leukodystrophy (MLD) and is now registered as a pharmaceutical product. More recently, HSC-GT has also shown promising results in patients with Hurler’s syndrome. Here, we report on the treatment for MLD currently being used in clinical practice and the gene therapy for MLD being studied at Nippon Medical School.