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The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
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Obstetrics and Gynegology2025№12

Principles for organizing a preclinical study of autologous CD34+ cells modified to express arylsulfatase A for the treatment of metachromatic leukodystrophy

DOI
https://dx.doi.org/10.18565/aig.2025.326

Iurova M.V., Popov K.V., Shevtsova Yu.A., Pavlovich S.V.

1) Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia

Metachromatic leukodystrophy (MLD) is an orphan autosomal recessive lysosomal disorder belonging to the group of storage diseases. It is caused by pathogenic variants of the ARSA gene encoding the enzyme arylsulfatase A (ASA) which lead to a decrease or absence of the gene activity and the subsequent accumulation of sulfatides (sulfate-containing glycosphingolipids) in the central and peripheral nervous system, primarily in membrane structures. This causes neurodegeneration, manifesting as progressive motor and cognitive impairment. There are currently no registered treatment options for MLD in the Russian Federation. Treatment is limited to supportive methods (e.g., physical therapy, muscle relaxants, pain medications) aimed at preventing complications and maintaining patients’ quality of life and hematopoietic stem cell transplantation from a healthy donor. This analytical review describes the methodology used in the organization of a preclinical trial of ASA-expressing CD34+ hematopoietic stem cell transplantation as a potential treatment for MLD. The review also presents regulatory requirements for validating results obtained in biological models. It outlines the steps involved in creating autologous stem cells to achieve an optimal in vivo outcome, namely, maintaining the efficacy of gene therapy obtained in preclinical studies when used in a human population.
Conclusion: CD34+-ARSA therapy is a rational and scientifically validated approach to long-term correction of enzyme deficiency and stabilization of the course of the disease.

Authors’ contributions: All the authors contributed equally to the preparation of this article: Iurova M.V., Popov K.V., Shevtsova Yu.A., Pavlovich S.V. – developing the concept of the article, obtaining and analyzing the actual data, writing and editing the text of the article, checking and approving the text of the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was carried out within the framework of the state assignment of the Ministry of Health of the Russian Federation No.123020800103-6. 
For citation: Iurova M.V., Popov K.V., Shevtsova Yu.A., Pavlovich S.V. Principles for organizing a preclinical study of autologous CD34+ cells modified to express arylsulfatase A for the treatment of metachromatic leukodystrophy. 
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (12): 5-18 (in Russian)
https://dx.doi.org/10.18565/aig.2025.326

Keywords

autologous hematopoietic therapy
autologous cells
arylsulfatase A
biodistribution
hematopoietic stem cells
gene therapy
genotoxicity
preclinical studies
metachromatic leukodystrophy
lentiviral vector
ARSA
CD34+ cells
Full text (in Russian)

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Received 11.11.2025

Accepted 28.11.2025

About the Authors

Mariia V. Iurova, PhD, obstetrician-gynecologist, oncologist, Senior Researcher at the Scientific Polyclinic Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4; Teaching Assistant at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Vocational Education, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), m_yurova@oparina4.ru, https://orcid.org/0000-0002-0179-7635
Konstantin V. Popov, PhD, Head of the Laboratory for Personalized Medicines, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, k_popov@oparina4.ru, https://orcid.org/0000-0002-3436-3235
Yulia A. Shevtsova, Junior Researcher at the Laboratory of Cell Technologies, Institute of Translational Medicine, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, yu_shevtsova@oparina4.ru,
https://orcid.org/0000-0003-4780-341X
Stanislav V. Pavlovich, PhD, Scientific Secretary, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4; Professor at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Vocational Education, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), s_pavlovich@oparina4.ru,
https://orcid.org/0000-0002-1313-7079
Corresponding author: Mariia V. Iurova, m_yurova@oparina4.ru
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