Advances In Hematopoietic Stem Cell Based Gene Therapy For The Treatment of Metachromatic Leukodystrophy

Dr. Alessandra Biffi, of the San Raffaele Scientific Institute, Milan, Italy, reported on her group’s advances in hematopoietic stem cell based gene therapy for the treatment of metachromatic leukodystrophy.

Metachromatic Leukodystrophy (MLD) is a demyelinating disease due to inherited deficiency of arylsulfatase A (ARSA). In the absence of effective therapies, MLD is a disease with an urgent medical need. This is particularly important, since donor hematopoetic stem cell (HSC) transplant in MLD has met with mixed results. In a mouse model, ARSA can be transplanted to the central nervous system. Specifically, the ARSA gene was transplanted to HSC of MLD mice. Then the modified HSCs were transplanted back to the MLD mice. After this treatment, the manifestations of MLD were corrected. Bboth the feasibility and safety of this therapeutic strategy were tested in a pre-clinical model. Using HSCs from human MLD patients, a similar strategy has successfully corrected the ARSA deficiency. These data have provided the basis for the next step, giving the treated HSCs back to an MLD patient. This clinical trial of HSC gene therapy for the treatment of MLD patients is expected to start by the second quarter of 2009. As in the mouse model, the protocol is based on isolating HSCs from the MLD patients, transplanting the normal ARSA gene into the HSCs, then giving the cells back to the patient. This strategy is expected to avoid the potential complications of graft vs. host disease and to achieve sustained long term ARSA expression in MLD patients.