CLINICAL TRIAL

Thymidine for Mitochondrial DNA Depletion Syndrome 2 Myopathic Type

EnrollingByInvitation · Any Age · All Sexes · New York, NY

This study is evaluating whether a treatment with nucleotide precursors can help patients with mitochondrial DNA depletion syndrome.

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About the trial for Mitochondrial DNA Depletion Syndrome 2 Myopathic Type

Eligible Conditions
Mitochondrial DNA Depletion Syndrome 2 Myopathic Type · Thymidine Kinase 2 Deficiency

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.

Main TreatmentA portion of participants receive this new treatment to see if it outperforms the control.
Thymidine
DRUG
Control TreatmentAnother portion of participants receive the standard treatment to act as a baseline.

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.

Inclusion & Exclusion Checklist
Mark “yes” if the following statements are true for you:
Genetically confirmed diagnosis of TK2 deficiency
Deemed by principle investigator to be symptomatic with TK2 deficiency
Single gene disease; absence of polygenic disease
Hematocrit within normal range for age group
Patient or patient's guardian able to consent and comply with protocol requirements
Presence of caregiver to ensure study compliance (if needed)
Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator)
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Odds of Eligibility
Unknown<50%
Be sure to apply to 2-3 other trials, as you have a low likelihood of qualifying for this one.Apply To This Trial

Approximate Timelines

Please note that timelines for treatment and screening will vary by patient
Screening: ~3 weeks
Treatment: varies
Reporting: Up to 60 months
Screening: ~3 weeks
Treatment: Varies
Reporting: Up to 60 months
This trial has approximate timelines as follows: 3 weeks for initial screening, variable treatment timelines, and reporting: Up to 60 months.
View detailed reporting requirements
Trial Expert
Connect with the researchersHop on a 15 minute call & ask questions about:
- What options you have available- The pros & cons of this trial
- Whether you're likely to qualify- What the enrollment process looks like

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.

euro Quality of Life (Neuro-QoL) in adults
UP TO 60 MONTHS
Neuro Quality of Life (Neuro-QoL) short forms will be used to assess effects of muscle weakness on motor function and activities of daily living. In adults, Lower and Upper Extremity scales will be assessed (0-80 points with higher scores indicating better function).
UP TO 60 MONTHS
Alanine aminotransferase
UP TO 60 MONTHS
Number of participants with treatment-related elevated alanine aminotransferase (ALT) serum level relative to upper limit of normal (expressed as ratios) grade 3 or higher as defined by CTCAE 4.03.
UP TO 60 MONTHS
Aspartate aminotransferase
UP TO 60 MONTHS
Number of participants with treatment-related elevated aspartate aminotransferase (AST) serum level relative to upper limit of normal (expressed as ratios) grade 3 or higher as defined by CTCAE 4.03.
UP TO 60 MONTHS
Hammersmith Functional Motor Scale Expanded (HFMSE)
UP TO 60 MONTHS
Hammersmith Functional Motor Scale Expanded (HFMSE) score (0-66 point range with higher scores indicating better function) will be measured in subjects >1 year-old.
UP TO 60 MONTHS
Electrocardiogram
UP TO 60 MONTHS
Number of patients with treatment related electrocardiogram (ECG) QT corrected interval (QTc) grade 3 or higher as defined by CTCAE version 4.03.
UP TO 60 MONTHS
Gamma-glutamyltransferase
UP TO 60 MONTHS
Number of participants with treatment-related elevated gamma-glutamyltransferase (GGT) serum level relative to upper limit of normal (expressed as ratios) grade 3 or higher as defined by CTCAE 4.03.
UP TO 60 MONTHS
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Who is running the study

Principal Investigator
M. H.
Prof. Michio Hirano, MD
Columbia University

Patient Q & A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer

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.

Anonymous Patient Answer
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