Research Highlights

Gene therapy delays childhood neurodegenerative disease

Published online 22 July 2013

Sara Osman

Metachromatic leukodystrophy (MLD) is a fatal neurodegenerative disorder that first appears in young children. It is caused by a deficiency in the enzyme Arylsulfatase A (ARSA) – which leads to a build up of sulfatides inside nerve cells. Sulfatides are thought to play a major role in the function and stability of myelin, the protective sheath that encases the axons of nerve cells.

A team of researchers led by Luigi Naldini, Alessandra Biffi and Eugenio Monitini at the San Raffaele Scientific Institute in Italy, and including Nabil Kabbara of the Rafic Hariri University Hospital in Beirut, have performed the first human clinical trials for a gene therapy targeting blood stem cells to treat MLD, publishing their results in Science.

The team extracted blood stem cells from the bone marrow of three children with MLD before the appearance of disease symptoms. They then infected these cells with lentivirus — a virus capable of integrating its genome with that of a host cell — engineered to contain the functional ARSA-producing gene. They then re-infused the now ARSA-corrected cells back into the patients.

The disease has not appeared or progressed by 7 to 12 months from the expected age of disease manifestation in all three patients. These results suggest using lentivirus to target blood stem cells is a promising approach for gene therapy, and a promising treatment for MLD.


  1. Biffi, A. et al. Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy. Science (2013) doi:10.1126/science.1233158