Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

Frontiers in Medicine

article

Alisa A. Shaimardanova¹  Daria S. Chulpanova²  Valeriya V. Solovyeva¹  Aysilu I. Mullagulova¹  Kristina V. Kitaeva¹  Cinzia Allegrucci³  Albert A. Rizvanov¹ 

[1] Institute of Fundamental Medicine and Biology, Kazan Federal University;Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences;School of Veterinary Medicine and Science (SVMS) and Biodiscovery Institute, University of Nottingham, United Kingdom

关键词: lysosomal storage diseases;    metachromatic leukodystrophy;    arylsulfatase A;    sulfatide;    replacement therapy;    gene therapy;    bone marrow transplantation;    mesenchymal stem cells;   

DOI  :  10.3389/fmed.2020.576221

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY