Learn The BasicsThere is currently no cure for thymidine Kinase 2 deficiency (TK2d), an ultra-rare and fatal mitochondrial disease mainly manifesting as progressive muscle weakness.
The U.S. Food and Drug Administration approved Kygevvi (doxecitine and doxribtimine) powder in November 2025 to treat patients who showed TK2d symptoms at or before age 12. Researchers are also studying the use of gene therapy alone and in combination with nucleoside therapy to treat TK2d.
Aside from therapeutic approaches, there are also supportive care methods that can improve patients’ quality of life and help manage the symptoms of the disease.
Kygevvi (doxecitine and doxribtimine) powder
Kygevvi (doxecitine and doxribtimine) powder, also known as nucleoside therapy, consists of two oral pyrimidine deoxynucleosides in equal parts: deoxycytidine (dC) and deoxythymidine (dT), which are the essential building blocks of DNA. They help maintain and replicate DNA and are normally recycled inside the mitochondria through the action of the TK2 enzyme.
In patients with TK2d, this enzyme is deficient due to a mutation or change in the gene coding for it, the recycling cannot be done properly.
Nucleoside therapy aims to bypass this step by providing the body with the necessary building blocks of DNA. The aim of this is that mitochondrial DNA maintenance and replication can be restored.
The therapy has already been tested in patients with TK2d and shown positive results. The efficacy was established based on data from one phase 2 clinical study, two retrospective chart review studies and an expanded access program.
Results from a clinical trial also showed that the approach was associated with improved survival in patients with TK2d. It also led to functional stabilization or improvement in motor function, respiration and feeding. However, very little is currently known about the potential effects of nucleoside therapy on the specific symptoms of the disease and patients’ quality of life.
Gene therapy
Another potential therapeutic approach for TK2d is gene therapy.
This approach makes use of viral vectors or “vessels” to deliver a healthy copy of the gene that codes for the TK2 enzyme to the body. The aim is to ensure cells make enough functional TK2 enzyme by themselves, thereby addressing the root cause of the disease.
This approach has been successfully tested in animal models of the disease, which showed that enzyme activity was restored in most tissues and the progression of the disease was delayed.
A combination approach of gene therapy and nucleoside therapy has also shown promise in preclinical studies with improved outcomes, including better physical growth and overall survival. This approach may be the way forward for the treatment of TK2d in the future.
Supportive care approaches
The supportive care approaches for TK2d aim to reduce disease burden and improve quality of life.
They include ventilatory care to support breathing, tube feeding to ensure adequate nutrition and reduce the risk of aspiration and lung infections and physical and occupational therapy to manage muscle weakness, increase range of motion and support patients with the use of assistive mobility devices like a wheelchair.
Patients may also be given a “mitochondrial cocktail,” which includes vitamins and supplements commonly used by patients diagnosed with mitochondrial diseases.