Gene therapy in advanced metachromatic leukodystrophy: tempering expectations

The Metachromatic Leukodystrophy Initiative (MLDi) critically responds to the findings of Zhang et al. on lentivirus-modified hematopoietic stem cell gene therapy in three metachromatic leukodystrophy (MLD) patients, urging caution in interpreting claims of clinical improvement. While Zhang et al. report stabilization or even improvement in two patients with advanced disease symptoms, MLDi emphasizes that the study lacks key clinical details—such as comprehensive assessments of cognition, motor, and speech function—needed to substantiate these claims. The third patient, diagnosed at an early symptomatic stage, does not represent outcomes for advanced-stage disease. MLDi also raises concerns over data gaps, including the unclear definition of "advanced disease" and the absence of outcomes for other treated patients. Previous research on hematopoietic stem cell transplantation and lentiviral-based gene therapy underscores the importance of early intervention for optimal outcomes in MLD.

In conclusion, MLDi stresses that the conclusions drawn by Zhang et al. may not align with current best practices and could risk creating false hope for MLD families. The work entitled “ Gene therapy in advanced metachromatic leukodystrophy: tempering expectations ” was published on Protein & Cell (published on Nov. 28, 2024).