Research Information System
28th International Congress of the World Muscle Society , South Carolina, United States Of America, 3 - 07 October 2023, vol.33, pp.184, (Summary Text)
Deoxynucleoside therapy for late onset thymidine kinase 2 deficiency patients
H Durmus Tekce ,A. Gedikbası, S. Ceylaner, H. Demirci, A. Cakar, S. Mergen, E. Kıyan, Y. Parman
Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
Recessive mutations in the TK2 which encodes for mitochondrial thymidine kinase, cause a rare mitochondrial depletion/multiple deletions syndrome. Late-onset TK2 deficiency is very rare and usually manifests as myopathy. TK2 phosphorylates the nucleosides deoxycytidine (dC) and deoxythymidine (dT) to generate deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP). These pyrimidine deoxynucleoside monophosphates are subsequently converted to deoxynucleoside triphosphates required for mitochondrial DNA (mtDNA) replication and maintenance. Deoxynucleoside therapy is currently under investigation. There was only one observational multicenter study describing the results of this new experimental therapy previously. We administered deoxynucleoside monophosphates and deoxynucleoside to three late onset TK2-deficient patients under a compassionate use program at the Department of Neurology, Istanbul Faculty of Medicine, Istanbul University. FDA and Ministry of Health of Turkey approved the compassionate use treatment. Deoxynucleoside monophosphate and deoxynucleoside therapies have not been approved for the treatment of thymidine kinase 2 deficiency. We obtained signed informed consent for the treatment from all patients. All patients underwent motor assessments using manual muscle testing (MMT, 19 muscles), 6-minute walk test (6MWT) and Hammersmith Functional Motor Scale (HFMS). Routine laboratory test, forced vital capacity (sitting and upright) and BMI were also recorded. The mean age of onset was 17 years (ranges 14-24 years). The mean duration of disease was 10.6 years (range 7 to 14 years). The distance walked improved in all, mean baseline 6MWT distances was 153m, mean 6MWT distance was 273m after 3 months of treatment and 350m after 6 months of treatment. Mean FVC 1 year prior to the treatment was 41%, 37% at baseline, 44% after 3 months and 50% after 6 months. Mean HFMS was 34.7 at baseline, 41.7 at 3rd month and 47.7 at 6th month of treatment. Mean FSS score was reduced by 10 points (from a baseline of 57.3) after 6 months of treatment. All patients gained weight, mean BMI was 15.5 at the baseline and 19 after 6 months of treatment. No treatment related serious adverse event was observed. Our data indicates favorable clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for late onset TK2 deficiency. http://dx.doi.org/10.1016/j.nmd.2023.07.461