Frameless stereotactic infusion of gene therapy into the putamen for AADC deficiency in children: technical and organizational aspects of implementation in Russia

Dmitriy A. Reshchikov; Рещиков Дмитрий Александрович; R. B. Mai; Маи Р. Б.; S. V. Mikhaylova; Михайлова С. В.; S. V. Gorelikov; Гореликов С. В.; Е. Yu. Zakharova; Захарова Е. Ю.; E. E. Petryaykina; Петряйкина Е. Е.; E. A. Putilina; Путилина Е. А.; V. V. Palm; Пальм В. В.

doi:10.17650/2222-8721-2025-15-4-10-16

Frameless stereotactic infusion of gene therapy into the putamen for AADC deficiency in children: technical and organizational aspects of implementation in Russia

Authors: Reshchikov D.A.¹, Mai R.B.¹, Mikhaylova S.V.¹, Gorelikov S.V.¹, Zakharova Е.Y.², Petryaykina E.E.¹, Putilina E.A.¹, Palm V.V.¹
Affiliations:
1. Russian Children’s Clinical Hospital – a branch of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
2. Research Centre for Medical Genetics
Issue: Vol 15, No 4 (2025)
Pages: 10-16
Section: ORIGINAL REPORTS
Published: 06.03.2026
URL: https://nmb.abvpress.ru/jour/article/view/679
DOI: https://doi.org/10.17650/2222-8721-2025-15-4-10-16
ID: 679

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Abstract

Aim. To present the authors’ experience in implementing a frameless stereotactic infusion technique of a gene preparation using an adeno-associated vectored virus into the subcortical structures of the brain in children with aromatic L-amino acid decarboxylase deficiency (AADCd), with an emphasis on technical and organizational aspects.

Materials and methods. From November 2024 to December 2025, six bilateral infusions of eladocagen exuparvovec (Upstaza^®) were administered into the putamen of children with genetically confirmed AADCd in the Department of Pediatric Neurosurgery of the Russian Children’s Clinical Hospital. The key stages of patient selection, regulatory support, preoperative planning based on brain magnetic resonance imaging data, features of frameless navigation, the Z-shaped convection-enhanced infusion technique, and measures for preventing intra- and postoperative complications are described. The analysis of clinical outcomes is deliberately not presented in this work and is planned for a separate publication after increasing the sample size and follow-up observation.

Results. In all 6 cases, accurate drug delivery to the putamen was ensured in accordance with preoperative planning, and no intraoperative complications were observed. Early postoperative magnetic resonance imaging monitoring revealed no clinically significant hemorrhagic or ischemic brain damage. In all cases, improvements in motor and autonomic symptoms of varying severity were noted during the first months of follow-up.

Conclusion. The presented experience demonstrates the technical feasibility and safety of frameless stereotactic gene therapy for AADCd in children in a Federal Center setting. The proposed method can serve as the basis for a national treatment protocol for AADCd and the establishment of a reference center for gene therapy for central nervous system diseases.

Keywords

aromatic L-amino acid decarboxylase deficiency deficiency, gene therapy, oculogyric crisis, frameless stereotactic surgery, putamen infusion, pediatric neurosurgery, eladocogen exuparvovec

References

Wassenberg T., Molero-Luis M., Jeltsch K. et al. Consensus guideline for the diagnosis and treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis 2017;12(1):12. doi: 10.1186/s13023-016-0522-z
Brun L., Ngu L.H., Keng W.T. et al. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology 2010;75(1):64–71. doi: 10.1212/WNL.0b013e3181e620ae
Hwu W.L., Muramatsu S., Tseng S.H. et al. Gene therapy for aromatic L-amino acid decarboxylase deficiency by AAV2 vector delivery to the putamen. Mol Ther 2012;20(1):131–8. doi: 10.1038/mt.2011.204
Chien Y.H., Lee N.C., Tseng S.H. et al. Long-term clinical and biochemical outcomes of AADC deficiency treated with gene therapy. Mol Genet Metab 2017;121(2):127–31. doi: 10.1016/j.ymgme.2017.04.005
Muramatsu S., Fujimoto K., Kato S. et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Ther 2010;18(9):1731–5. doi: 10.1038/mt.2010.135
Bradac O., Steklacova A., Nebrenska K. et al. Accuracy of VarioGuide frameless stereotactic system against frame-based stereotaxy: prospective, randomized, single-center study. World Neurosurg 2017;104:831–40. doi: 10.1016/j.wneu.2017.04.104
Mai R., Reshchikov D., Popov V. et al. Frameless intraputaminal delivery of gene therapy with eladocagene exuparvovec in patients with aromatic L-amino acid decarboxylase deficiency: safe and efficient results. Childs Nerv Syst 2025;41:346. doi: 10.1007/s00381-025-07020-y

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Frameless stereotactic infusion of gene therapy into the putamen for AADC deficiency in children: technical and organizational aspects of implementation in Russia

Full Text

Abstract

Keywords

About the authors

References

Supplementary files