The presence of autosomal recessive mutations in human thymidine kinase 2 (TK2) leads to TK2 deficiency, which typically presents as a progressive and fatal mitochondrial myopathy in infants and children. Protheragen is dedicated to providing comprehensive support to the scientific community in addressing this uncommon and severe mitochondrial disease.
Introduction to Thymidine Kinase 2 Deficiency
Thymidine kinase 2 deficiency (TK2d), also referred to as TK2 deficiency, is an extremely rare autosomal recessive syndrome characterized by a mutation in the TK2 gene within the nuclear DNA (nDNA). This specific gene encodes thymidine kinase 2 found in mitochondria, which is one of the essential enzymes involved in mitochondrial DNA synthesis, primarily affecting the proximal, bulbar, and facial muscles with significant respiratory involvement.
Research Progress of Kinase 2 Deficiency
The research on TK2D is primarily focused on comprehending the pathophysiology, clinical manifestations, and potential therapeutic interventions for this disorder. Investigations into TK2D have successfully identified over 30 pathogenic variants in the TK2 gene, with a majority of these being missense mutations that lead to functional loss of the TK2 enzyme. Consequently, this disruption significantly impacts mitochondrial DNA synthesis and maintenance.
Novel Diagnostic Methods of Thymidine Kinase 2 Deficiency
The diagnosis of TK2D is typically established through genetic testing, specifically by conducting mutation analysis of the TK2 gene. By employing whole exon sequencing and analyzing mitochondria-associated genes, a more precise diagnosis of TK2D can be achieved, even in cases where a muscle biopsy is not performed. Circulating biomarkers in the blood such as GDF-15 and/or FGF-21 can serve as supplementary diagnostic tools, offering additional insights into disease progression and treatment response.
Fig.1 Proposed TK2d diagnostic algorithm. (Domínguez-González, C., et al., 2021)
Novel Therapies of Thymidine Kinase 2 Deficiency
The initial nucleoside therapy employed in the treatment of TK2D has demonstrated success in murine models and exhibited efficacy in human clinical trials. This therapeutic approach primarily entails the utilization of nucleosides (dT/dC) to reinstate mitochondrial function by replenishing the availability of deoxynucleotide triphosphate (dNTPs) necessary for mitochondrial DNA replication. MT1621, a nucleoside medication comprising two nucleosides (dC and dT), serves as a therapeutic strategy for TK2D.
Fig.2 Pharmacological mechanism of nucleoside therapy in TK2d. (Domínguez-González, C., et al., 2021)
Our Services
As a leading preclinical contract research organization (CRO) specializing in mitochondrial diseases, Protheragen is dedicated to delivering comprehensive research support and tailored solutions to esteemed research institutions and pharmaceutical companies. Our extensive range of specialized research services focuses on TK2D, enabling our clients to gain profound insights into the disease's pathogenesis and explore potential therapeutic interventions.
Our Advantages
The TK2d research services provided by Protheragen offer comprehensive support, ranging from the development of diagnostic tools to the discovery of therapeutics. We will collaborate closely with you to address this significant health challenge. If you are interested in our services or have any inquiries, please do not hesitate to contact us.
Reference
- Domínguez-González, C.; et al. (2021). Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency. Orphanet journal of rare diseases, 16(1), 407.
