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Based on the age at onset, the disease is usually classified into three forms: the late\u2010infantile form, which manifests in the second year of life; the juvenile variants (onset between 4 and 12 years), which are subdivided into early\u2010juvenile (EJ, onset before 6 years) and late\u2010juvenile (LJ, onset after 6 years); and the adult form (onset after 12 years of age). Currently, there is no efficient therapy for the late\u2010infantile form of MLD (50% of the patients), death occurring within a few years after onset of neurological symptoms. Allogeneic haematopoietic cell transplantation (HCT), when performed at a very early stage of the disease, may improve selected patients with juvenile or adult forms of MLD. As with other lysosomal storage diseases, the physiopathology of MLD is poorly understood. Demyelination is the main pathological finding, but substantial storage of sulfatides in neurons also occurs, and may contribute to the clinical phenotype. The physiopathological process leading to neuronal and glial cell degeneration and apoptosis involves accumulation of undegraded sulfatides but also secondary abnormalities (storage\/mislocalization of unrelated lipids, inflammatory processes). This review summarizes the recent advances in the understanding of the physiopathology of MLD and the new therapeutic perspectives currently under preclinical investigation, including enzyme replacement therapy, gene therapy and cell therapy.<\/jats:p>","DOI":"10.1007\/s10545-007-0540-z","type":"journal-article","created":{"date-parts":[[2007,3,8]],"date-time":"2007-03-08T11:17:33Z","timestamp":1173352653000},"page":"175-183","source":"Crossref","is-referenced-by-count":73,"title":["Enzyme, cell and gene\u2010based therapies for metachromatic leukodystrophy"],"prefix":"10.1002","volume":"30","author":[{"given":"C.","family":"Sevin","sequence":"first","affiliation":[{"name":"University Ren\u00e9\u2010Descartes Paris 5, INSERM U745 Paris France"},{"name":"Department of Pediatric Neurology H\u00f4pital Saint\u2010Vincent de Paul 82 avenue Denfert\u2010Rochereau Paris 75014 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