Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency

Summary

The purpose of this clinical trial is to evaluate the efficacy and safety of Doxecitin and Doxribtimine (dC+dT) in adult participants with thymidine kinase 2 (TK2) deficiency attended in the Neuromuscular Unit of '12 de Octubre' Hospital. The main questions it aims to answer are: * Is dT+dC effective in the treatment of the adult participants with TK2 deficiency? * Is dT+dC safe in the treatment of adult participants with TK2 deficiency? Researchers will evaluate the effectiveness of the treatment doxecitin and doxribthymine in adult participants with TK2 deficiency. In addition, the mitochondrial DNA levels before and after treatment (extracted from the muscle and from uroepithelial cells) of these participants will be also studied.

Timeline

Start

2025-01-01

Primary completion

2027-01-31

Completion

2027-12-31

Publications

• Background Dominguez-Gonzalez C, Badosa C, Madruga-Garrido M, Marti I, Paradas C, Ortez C, Diaz-Manera J, Berardo A, Alonso-Perez J, Trifunov S, Cuadras D, Kalko SG, Blazquez-Bermejo C, Camara Y, Marti R, Mavillard F, Martin MA, Montoya J, Ruiz-Pesini E, Villarroya J, Montero R, Villarroya F, Artuch R, Hirano M, Nascimento A, Jimenez-Mallebrera C. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy. Sci Rep. 2020 Jun 22;10(1):10111. doi: 10.1038/s41598-020-66940-8.
• Background Berardo A, Dominguez-Gonzalez C, Engelstad K, Hirano M. Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. J Neuromuscul Dis. 2022;9(2):225-235. doi: 10.3233/JND-210786.
• Background Bermejo-Guerrero L, Hernandez-Voth A, Serrano-Lorenzo P, Blazquez A, Martin-Jimenez P, Martin MA, Dominguez-Gonzalez C. Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report. Mitochondrion. 2024 May;76:101879. doi: 10.1016/j.mito.2024.101879. Epub 2024 Apr 9.
• Background Dominguez-Gonzalez C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodriguez FJ, Donati MA, Kleinsteuber K, Marti I, Martin-Hernandez E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Alvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Marti R, Paradas C, Hirano M. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Ann Neurol. 2019 Aug;86(2):293-303. doi: 10.1002/ana.25506. Epub 2019 Jun 17.

Drugs

Indications