Abstract
Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency. ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively. The severity of clinical course in metachromatic leukodystrophy is determined by the residual ARSA activity, depending on the type of mutation. Currently, there is no effective treatment for this disease. Clinical cases of bone marrow or cord blood transplantation have been reported, however the therapeutic effectiveness of these methods remains insufficient to prevent aggravation of neurological disorders. Encouraging results have been obtained using gene therapy for delivering the wild-type ARSA gene using vectors based on various serotypes of adeno-associated viruses, as well as using mesenchymal stem cells and combined gene-cell therapy. This review discusses therapeutic strategies for the treatment of metachromatic leukodystrophy, as well as diagnostic methods and modeling of this pathology in animals to evaluate the effectiveness of new therapies.
Highlights
Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary neurodegenerative disease belonging to the group of lysosomal storage diseases (LSDs)
The disease is characterized by the damage of the myelin sheath that covers most of the nerve fibers of the central (CNS) and peripheral nervous systems (PNS), resulting in progressive motor and cognitive impairment as clinical manifestations [2]
The results prove that this method minimizes the false-positive result in arylsulfatase A (ARSA) pseudodeficiency [27]
Summary
Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary neurodegenerative disease belonging to the group of lysosomal storage diseases (LSDs). AAVrh.10-ARSA more effectively infected PNS cells and reduced the sulfatide accumulation in the nervous system of MLD model mice compared to AAV9-ARSA
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