The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.

Treatment effects of OTL-200, a hematopoietic stem cell-based gene therapy, were found to be durable and clinically relevant on both motor function as well as cognitive development in patients with early-symptomatic early-juvenile (ES-EJ) metachromatic leukodystrophy (MLD) who were treated prior to moving into the rapidly progressive phase of the disease, according to research presented the 17th Annual WORLDSymposium.

Currently, there are no approved treatments for MLD, a lysosomal storage disease caused by a deficiency in arylsulfatase A (ARSA). “OTL-200 consists of autologous CD34+ cells transduced ex vivo with a lentiviral vector encoding for the functional human ARSA gene, infused intravenously following busulfan conditioning,” the authors explained. Results assessing the long-term efficacy and safety of OTL-200 in 33 patients with early-onset MLD were previously reported.

In this additional analysis of OTL-200, the extended follow-up of 8 ES-EJ MLD patients (mean follow-up, 5.30 years; range, 0.64-7.93) was presented. The authors reported, “As previously reported, 2 ES-EJ patients died due to disease progression 8- and 15-months post-treatment, deemed unrelated to OTL-200.” Of the 6 surviving patients, 1 experienced motor deterioration after being treated during a phase of  rapid disease progression while the other 5 (follow-up: 4.13-7.93 years) displayed meaningful clinical responses in both gross motor function as well as cognition compared to 12 EJ natural history (NH) patients who were not treated.

“Treatment differences in mean gross motor function measure score versus the age-matched NH group was above the threshold (10%) pre-specified in the study protocol at year 2 (n=6; 28.7%; 95% CI, 14.1-71.5) and was larger at year 5 (n=5; 42.9%; 95% CI, -0.5, 86.3),” the study authors reported. Findings revealed that 5 of the 6 surviving patients maintained locomotion or were able to sit without support 4 years after disease onset.

Additionally, 4 of the treated patients displayed normal cognitive development during the follow-up period while all NH patients were found to have significant cognitive decline at comparable chronological ages. The authors added, “Relevant treatment benefits were particularly observed when EJ patients were treated before the onset of cognitive deterioration (IQ ≥85) while maintaining the ability to walk independently (GMFC-MLD ≤1).”


Fumagalli F, Calbi V, Sessa M, et al. Lentiviral hematopoietic stem and progenitor cell gene therapy provides durable clinical benefit in early-symptomatic early-juvenile metachromatic leukodystrophy. Presented at: 17th Annual WORLDSymposium; February 8-12, 2020. Poster #075.