Stem Cell Gene Therapy Shows Promise for Metachromatic Leukodystrophy

Francesca Fumagalli, PhD, Researcher of Cardiovascular Medicine at Istituto di Ricerche Farmacologiche Mario Negri (IRCCS), discusses positive results of a study of lentiviral hematopoietic stem cell gene therapy for the treatment of metachromatic leukodystrophy (MLD).

MLD is a lysosomal storage disorder caused by arylsulfatase A (ARSA) deficiency. It is characterized by the accumulation of sulfatides in cells which largely affects myelin producing cells. This leads to the progressive destruction of white matter throughout the nervous system.

Affected individuals show progressive deterioration of cognitive ability, motor, and sensory functions. Eventually they lose awareness of their surroundings and become unresponsive. Without treatment, the disease is fatal after a few years. Currently, there is no approved treatment.

Long-term safety and efficacy results in 33 early-onset MLD patients treated with investigational lentiviral hematopoietic stem cell gene therapy, OTL-200, was presented at WORLDSymposium 2020. At WORLDSymposium 2021, additional analysis with extended follow-up of 8 early-symptomatic early-juvenile MLD patients was presented. Five = of the eight treated patients (62.5%) maintained locomotive and/or sitting abilities versus 36% for untreated natural history patients from the original study. Additionally, four out of the eight treated patients showed normal cognitive development throughout follow-up. In contrast, all natural history patients from the original study exhibited significant cognitive decline at comparable chronological ages. Relevant treatment benefits were particularly observed when patients were treated before the onset of cognitive deterioration (IQ ≥ 85) and while maintaining the ability to walk independently.

These results suggest durable and clinically relevant treatment effects of OTL-200 on motor function and cognitive development in ES-EJ MLD patients treated before entering the rapidly progressive phase of the disease.

To learn more about MLD and other lysosomal storage disorders, visit checkrare.com/diseases/lysosomal-storage-disorders/