1. ¹San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy
2. ²BMT Unit, Pediatric Department of Milano-Bicocca University, San Gerardo Hospital, Monza, Italy
3. ³Department of Neurology, San Raffaele Scientific Institute, Milan, Italy

Correspondence: Dr A Rovelli, Centro Trapianto di Midollo Osseo, Clinica Pediatrica dell'Università di Milano-Bicocca, Ospedale San Gerardo, Via Pergolesi 33, Monza 20052, Italy. E-mail: attilio.rovelli@pediatriamonza.it

Abstract

Nowadays, different treatment options are available for an extending list of lysosomal storage diseases (LSDs). Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. Enzyme replacement therapy has been developed recently for MLD, and a Phase I/II trial is ongoing. However, the blood-brain barrier limits the access of the recombinant product to the nervous tissues. Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a quantitatively more effective source of functional enzyme than normal donor cells when transplanted in patients with MLD, thus possibly overcoming the limits of HSCT. Moreover, autologous transplantation might be associated with a significantly reduced transplant-related morbidity and TRM avoiding the risk of GVHD. Therefore, such a gene therapy strategy could represent a significant advance in comparison to conventional allogeneic HSCT.