Innovative medicines for Rett syndrome therapy: Present and future
https://doi.org/10.66825/2949-4664-apps-3-4-77-82
Abstract
The Rett syndrome (RTT, RS, MIM #312750) is a severe progressive hereditary disease that leads to impaired development of the nervous system. This disorder, affecting primarily girls, remains one of the most common genetic causes of severe mental retardation in female patients. For decades, the management of RS patients has been largely limited to palliative and multidisciplinary care aimed at alleviating the most severe clinical signs threatening the quality of life. These strategies, however, do not target the pathogenetic mechanisms of the disease, thus failing to slow the progression of neurological symptoms and modify the RS course. This underscores the importance of creating disease-modifying therapeutic approaches. The present systematic review analyzes current international trends in the development and registration of medicines for RS treatment, along with the data on the existing disease-modifying drugs and those currently undergoing clinical studies. Such medicines form a new paradigm in the management of RS patients.
About the Author
L. A. Pak
Research Clinical Institute of Childhood
Russian Federation
Competing Interests:
Russian Federation
Lolita A. Pak, Dr. Sci. (Med.), Prof., Deputy Director for Clinical and Organizational Work, Department of Clinical Genetics and Orphan Diseases
24A, Kominterna str., Mytischi, 141009
Competing Interests:
The author declares no conflict of interest.
References
1. Gold W. A., Percy A. K., Neul J. L. et al. Rett syndrome. Nat. Rev. Dis. Primers. 2024;10(84). doi: 10.1038/s41572-024-00568-0.
2. Laurvick C. L. et al. Rett syndrome in Australia: a review of the epidemiology. J. Pediatr. 2006;148:347–352. doi: 10.1016/j.jpeds.2005.10.037.
3. Rett A. On a unusual brain atrophy syndrome in hyperammonemia in childhood [German]. Wien. Med. Wochenschr. 1966;116:723–726.
4. Hagberg B., Aicardi J., Dias K. & Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann. Neurol. 1983;14:471–479. doi: 10.1002/ana.410140412.
5. Neul J. L. et al. Specific mutations in methyl-CpGbinding protein 2 confer different severity in Rett syndrome. Neurology. 2008;70:1313–1321. doi: 10.1212/01. wnl.0000291011.54508.aa.
6. Amir R. E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 1999;23:185–188. doi: 10.1038/13810.
7. Neul J. L. et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann. Neurol. 2010;68:944–950. doi: 10.1002/ana.22124.
8. Fu C., Armstrong D., Marsh E., Lieberman D., Motil K., Witt R., Standridge S., Nues P., Lane J., Dinkel T., Coenraads M., von Hehn J., Jones M., Hale K., Suter B., Glaze D., Neul J., Percy A., Benke T. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatr Open. 2020 Sep 13;4(1): e000717. doi: 10.1136/bmjpo-2020-000717.
9. Kennedy M., Glass L., Glaze D. G., Kaminsky S., Percy A. K., Neul J. L., Jones N. E., Tropea D., Horrigan J. P., Nues P., Bishop K. M., Youakim J. M. Development of trofinetide for the treatment of Rett syndrome: from bench to bedside. Front Pharmacol. 2024 Jan 22;14:1341746. doi: 10.3389/fphar.2023.1341746.
10. https://acadia.com/en-us/pdf/our-medicines/daybue-prescribing-information.pdf [дата обращения: 12.10.2025].
11. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-rett-syndrome [дата обращения: 12.10.2025].
12. https://clinicaltrials.gov/study/NCT04181723 [дата обращения: 12.10.2025].
13. Neul J. L. et al. Neul. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nature Medicine. June 2023;29:468–1475. doi: 10.1038/s41591-023-02398-1.
14. https://daybuehcp.com/cgi-i/ [дата обращения: 12.10.2025].
15. Neul J. L. et al. A plain language summary of results from the LAVENDER study: trofinetide treatment for Rett syndrome. Future Rare Dis. 2023; FRD44. doi: 10.2217/frd-2023-0010.
16. https://clinicaltrials.gov/study/NCT04279314 [дата обращения: 12.10.2025].
17. Percy Alan K. et al. Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study. Med. September 13, 2024;5:1178–1189. Published by Elsevier Inc. doi: 10.1016/j.medj.2024.05.018.
18. https://clinicaltrials.gov/study/NCT04776746 [дата обращения: 12.10.2025].
19. Percy Alan K. et al. Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study. Med. October 11, 2024;5:1275–1281. Published by Elsevier Inc. doi: 10.1016/j.medj.2024.06.007.
20. Barrett A. et al. Assessing Experiences With Trofinetide for Rett Syndrome: Interviews With Caregivers of Participants in Clinical Trials. Clinical Therapeutics. 2025;47:181–188. doi: 10.1016/j.clinthera.2024.12.012.
21. https://clinicaltrials.gov/study/NCT04988867 [дата обращения: 12.10.2025].
22. Percy Alan K. et al. Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2–4 years with Rett syndrome. Med. 13 June 2025;6(6):100608. doi: 10.1016/j.medj.2025.100608.
23. https://clinicaltrials.gov/study/NCT04304482 [дата обращения: 12.10.2025].
24. https://clinicaltrials.gov/study/NCT03941444 [дата обращения: 12.10.2025].
25. https://euclinicaltrials.eu/ctis-public/view/2024–514684–26–00 [дата обращения: 12.10.2025].
26. https://clinicaltrials.gov/study/NCT06621043.
27. Keating B. A., Ogru Y., Duthy T. G., et al. Full-Spectrum Medicinal Cannabis Plant Extract 0.08 % THC (NTI164) Improves Symptoms of Rett Syndrome: An Open-Label Study. Journal of Paediatrics and Child Health. 2025:1–8, doi: 10.1111/jpc.70122.
28. https://clinicaltrials.gov/study/NCT07150013 [дата обращения: 10.10.2025].
29. https://clinicaltrials.gov/study/NCT05606614 [дата обращения: 10.10.2025].
30. https://clinicaltrials.gov/study/NCT06152237 [дата обращения: 10.10.2025].
31. https://clinicaltrials.gov/study/NCT06739434 [дата обращения: 10.10.2025].
32. https://clinicaltrials.gov/study/NCT06856759 [дата обращения: 10.10.2025]
33. Samanta D. Disease-modifying therapies for Rett syndrome: a review for neurologists. Front Neurol. 2026 Jan 20;17:1766679. doi: 10.3389/fneur.2026.1766679.
Review
For citations:
Pak L.A. Innovative medicines for Rett syndrome therapy: Present and future. Archives of Pediatrics and Pediatric Surgery. 2025;3(4):77-82. (In Russ.) https://doi.org/10.66825/2949-4664-apps-3-4-77-82
Views:
27
JATS XML
Email this article 