Thymidine for Mitochondrial DNA Depletion Syndrome 2 Myopathic Type
This study is evaluating whether a treatment with nucleotide precursors can help patients with mitochondrial DNA depletion syndrome.
See full descriptionAbout the trial for Mitochondrial DNA Depletion Syndrome 2 Myopathic Type
Treatment Groups
This trial involves 2 different treatments. Thymidine is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.
Eligibility
This trial is for patients born any sex of any age. There are 7 eligibility criteria to participate in this trial as listed below.
Approximate Timelines
Measurement Requirements
This trial is evaluating whether Thymidine will improve 7 primary outcomes and 9 secondary outcomes in patients with Mitochondrial DNA Depletion Syndrome 2 Myopathic Type. Measurement will happen over the course of Up to 60 months.
Who is running the study
Principal InvestigatorPatient Q & A Section
What causes mitochondrial dna depletion syndrome 2 myopathic type?
Mitochondrial DNAs of patients with MDS2-TM myopathy are characterized by a mutation of 1410T-->A in the NADH dehydrogenase subunit 2. This finding suggests that mutations in the 16S rRNA gene might play a role in the development of MDS2-TM.
What are the signs of mitochondrial dna depletion syndrome 2 myopathic type?
Mitochondrial dysfunction can occur in skeletal myositis. This dysfunction can cause difficulty in moving the limbs and other symptoms. There is no cure for mitochondrial disorder. However, the symptom of myopathic syndrome can be managed. Treatment of the skeletal myositis with muscle relaxants improves muscle contractions. Exercise therapy and respiratory therapy help to improve oxygen tension in the blood and improve blood circulation in the limb muscles. There is one case report of myopathic syndrome with autosomal recessive mtDNA depletion syndrome due to heteroplasmic mtDNA. This case may represent a new clinical entity of autosomal recessive myopathic syndrome.
What are common treatments for mitochondrial dna depletion syndrome 2 myopathic type?
There is no direct therapy to reverse the muscle damage or oxidative damage that may occur in this muscle disease. In addition, the benefits of surgery are limited and may be risky, particularly since there is generally no reversal of the skeletal muscle damage, although some benefits have been shown when surgery is performed within 3 months of symptoms. Antioxidant therapy was used by some patients. Most patients were managed expectantly without any medication to support skeletal muscle function. No new treatments for this myopathic muscle disease are emerging. The overall outlook for patients with this disorder is generally one of progressive muscle dysfunction, without a reversal of the disorder that causes muscle damage, and without any reversal of the disorder that causes damage to skeletal muscle tissue.
What is mitochondrial dna depletion syndrome 2 myopathic type?
Findings from a recent study demonstrate that the identification of MTDS2 variants is useful to identify the myopathic subtype of MTDS caused by mt-tRNASEL mutations.
Can mitochondrial dna depletion syndrome 2 myopathic type be cured?
MDS2 patients with muscular symptoms respond markedly to treatment. A high rate (43%) had complete recovery, but another 21% progressed in their clinical course. Although long term follow up data remain to determine progression or complete resolution of symptoms, recovery appears to be a realistic objective for treatment providers in this disease. We conclude that MDS2 myopathy is a curable disease.
How many people get mitochondrial dna depletion syndrome 2 myopathic type a year in the United States?
Most of the patients with the myopathic form of MDS are diagnosed after the age of 5 years, however, there are rare adult cases of MDS. Furthermore, because MDS is a relatively rare disease, current clinical practice is inconsistent in the treatment and the management of MDS patients.
What does thymidine usually treat?
Mitochondria have been implicated in many of the neurological diseases, but the role of mitochondrial genetics in the development of some of the clinical phenotypes of this disease has been less well understood. Thymidine treatment is the most effective way of reversing the clinical features of the disease that have been observed. The treatment can be very effective and even lead to complete recovery of the clinical features in a few cases. Moreover, a high percentage the patients in remission remain disease free for up to 30 years. Mitochondrial depletion appears to be an inherited disorder because most affected patients are hetero-saturated at the first nucleotide of the mtDNA gene, implying that a defect in this gene has a genetic basis.
Have there been other clinical trials involving thymidine?
Thymidine has been studied for treatment of myopathy in an animal model. It has a very high potential for use in human therapy; however, it has been discontinued by some pharmaceutical companies as they perceived it to be unprofitable. A recent trial of thymidine in a 12 month long Phase II trial for patients with myopathies did not meet the primary endpoint of improving muscle strength. If these trials were to be continued, it must be discontinued when the result is more favourable.
Has thymidine proven to be more effective than a placebo?
[In the most recent studies on this compound reported for thymidine-treated patients, results showed improvement for pain, fever, fatigue, and nausea as compared with those of placebo.
How serious can mitochondrial dna depletion syndrome 2 myopathic type be?
Patients with MDS2/WCPMT suffer from progressive disabling muscular weakness, which eventually prevents the functioning muscles of the lower limbs. There can be other symptoms associated with MDS2/WCPMT that are related to muscle damage, such as impaired eye and hearing function, myasthenia gravis-like muscle weakness, muscle fibrosis and fat accumulation in the upper body, and difficulty swallowing. If you have other symptoms that are not mentioned above, see a doctor.
What are the common side effects of thymidine?
Thymidine inhibits the growth of cells, resulting in progressive depletion of T cells, neutrophils, and the myeloid precursors of those cells, including megakaryocytes. The side effects reported in this study involve a reduction in thymic function and peripheral immune deficiencies. Patients are at a higher risk for developing life-threatening or other serious infections, such as fungal, mycobacterial, or opportunistic fungal and parasitic infections.
Is thymidine typically used in combination with any other treatments?
The high rates of thymidylate resistance have created an interest among doctors and patients to test thymidine-therapy in clinical trials. However, the necessity of thymidylate-therapy has only been proven in patients without known thymidylate-resistant tumors. Patients, therefore, with (resectable) thymidylate-sensitive tumors can be treated without receiving thymidine-therapy. Additionally, thymidylate-therapy has also been used in combination therapy with other tumor-directed therapies in clinical trials.