CLINICAL TRIAL IN METACHROMATIC LEUKODISTROPHY

Metachromatic leukodystrophy (MLD) is a rare, but severe disease characterized by signs and symptoms due to the involvement of the Central and Peripheral Nervous Systems, such as developmental delay or psychomotor regression, motor and swallowing difficulties, blindness and deafness, seizures, and weakness. Age of onset, evolution, and prognosis are highly variable but, in the majority of the cases, the disease is fatal few years after onset. No specific treatment is currently available. However, in early stages of the disease and in the milder variants, bone marrow transplantation has been shown to be effective in stabilizing or slowing the disease process. Because of the rarity of MLD, the variability within the different forms, and the paucity of clinical and instrumental records, it is not possible to precisely predict the course of individual children presenting with MLD, and this is an obstacle both to counseling, but also to the design of therapeutic intervention trials. In the past few years we have been involved in the management of patients with metabolic diseases and we are currently monitoring 12 MLD patients with a clinical and instrumental follow up. Moreover, our involvement in the creation of a network among some of the major institutes dealing with metabolic pediatric diseases in Italy will further increase the number of MLD patients referred to our Institute. We therefore plan to recruit six new patients per year reaching a total number of thirty patients by the end of the proposed grant. We plan to characterize the mutations causing the disease and the residual activity of the defective enzyme for each patient and to monitor them with clinical and instrumental follow up along the three year period. We think that a clinical study along the time course of metachromatic leukodystrophy is a fundamental prerequisite for defining new therapies and evaluating any potential benefits.