New therapeutic strategies for the treatment of metachromatic leukodystrophy


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Abstract

Metachromatic leukodystrophy is an autosomal recessive hereditary neurodegenerative disease belonging to the group of lysosomal storage diseases, which is characterized by the damage of the myelin sheath that covers most of the nerve fibers of the central and peripheral nervous systems. Metachromatic leukodystrophy caused by the deficiency of arylsulfatase A (ARSA) lysosomal enzyme (OMIM 250100) or sphingolipid activator protein B (SapB or saposin B) (OMIM 249900). Clinical manifestations of metachromatic leukodystrophy are progressive motor and cognitive impairment in patients. ARSA and SapB protein deficiency are caused by the mutations in the ARSA and PSAP genes, respectively. The severity of clinical signs in metachromatic leukodystrophy is determined by the residual ARSA activity, depending on the type of mutation. There is currently no effective treatment for this disease. Clinical cases of bone marrow or cord blood transplantation have been described, however, the therapeutic effectiveness of these methods remains insufficient to prevent aggravation of neurological disorders in patients. Encouraging results were 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 for this disease.

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A. A Shaimardanova

Kazan Federal University

Kazan, Russia

D. S Chulpanova

Kazan Federal University

Kazan, Russia

V. V Solovyeva

Kazan Federal University

Kazan, Russia

A. I Mullagulova

Kazan Federal University

Kazan, Russia

K. V Kitaeva

Kazan Federal University

Kazan, Russia

AA. A Rizvanov

Kazan Federal University

Email: rizvanov@gmail.com
Kazan, Russia

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