Metachromatic Leukodystrophy

Overview

Fatal progressive neurodegenerative disorder treated with hematopoietic stem cell gene therapy; clinical data showed treated patients halted disease progression and gained motor or cognitive milestones versus untreated controls who progressively lost function. Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder in which patients progressively lose the ability to walk and acquire milestones and eventually die; gene therapy patients showed halted disease progression and in most cases gained motor or cognitive milestones compared to untreated natural history controls. Marketing authorization for the MLD gene therapy was obtained with fewer than 30 patients, demonstrating that robust clinical evidence can support regulatory approval with very small cohorts in rare disease settings. (Segment 2 (05:00-10:00)) The first MLD patient seen at San Raffaele could not be treated because the disease had progressed too far, but the diagnosis enabled the family's younger sibling to be identified and treated presymptomatically, preventing neurological decline. The presymptomatically treated MLD patient is now an adult who walks, demonstrating that gene therapy can preserve motor function when given before symptom onset; the family regards the treatment day as a 'new birthday' reflecting its transformative impact. (Segment 6 (25:00-30:00))