Lorioli L.,San Raffaele Telethon Institute for Gene Therapy |
Lorioli L.,Pediatric Immunohematology Unit |
Lorioli L.,San Raffaele Scientific Institute |
Lorioli L.,Vita-Salute San Raffaele University |
And 4 more authors.
Expert Opinion on Orphan Drugs | Year: 2015
Metachromatic leukodystrophy (MLD) is a rare, fatal, inherited lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA). The enzymatic defect results in the accumulation of the ARSA substrate, mainly in myelin forming cells, leading to progressive demyelination and dysfunction in the CNS and peripheral nervous system. The severity of the disease and the absence of approved treatments stimulate testing innovative therapeutic strategies.Areas covered: Among diverse experimental approaches, hematopoietic stem cell (HSC) transplantation (HSCT) from healthy compatible donors, and very recently, gene therapy based on transplantation of autologous HSCs transduced with a lentiviral vector encoding for the ARSA cDNA have been applied to MLD patients. State of the development of these HSC-based strategies is here analyzed, based on a review of the scientific literature, focusing on the outcomes of allogeneic HSCT, and on its potential clinical benefit and limitations.Expert opinion: HSC-based approaches would require the evaluation of long-term follow-up on neurological and transplant-related outcomes of larger cohorts of patients, in order to rationally define indication to treatment for MLD patients. © 2015 Informa UK, Ltd.