Gene Therapy for Metachromatic Leukodystrophy (MLD)

A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic Leukodystrophy

This Phase I/II clinical trial consists of the application of lentiviral vector-based gene therapy to patients affected by Metachromatic Leukodystrophy (MLD), a rare inherited Lysosomal Storage Disorder (LSD) resulting from mutations in the gene encoding the Arylsulfatase A (ARSA) enzyme. The medicinal product consists of autologous CD34+ hematopoietic stem/progenitor cells in which a functional ARSA cDNA is introduced by means of 3rd generation VSV-G pseudotyped lentiviral vectors.

Inclusion Criteria:

• Pre-symptomatic MLD patients with the late infantile variant;
• Pre- or early-symptomatic MLD patients with the early juvenile variant;
• Patients for whom parental/guardian signed informed consent has been obtained.

Exclusion Criteria:

• HIV RNA and/or HCV RNA and/or HBV DNA positive patients;
• Patients affected by neoplastic diseases;
• Patients with cytogenetic alterations typical of MDS/AML;
• Patients with end-organ functions or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
• Patients enrolled in other trials/other therapeutic approaches that might become available;
• Patient who underwent allogeneic hematopoietic stem cell transplantation in the previous six months;
• Patient who underwent allogenic hematopoietic stem cell transplantation with evidence of residual cells of donor origin.