This trial is evaluating whether deoxycytidine and deoxythymidine will improve 1 primary outcome and 1 secondary outcome in patients with Mitochondrial Encephalomyopathies. Measurement will happen over the course of 26 weeks.
This trial requires 15 total participants across 2 different treatment groups
This trial involves 2 different treatments. Deoxycytidine And Deoxythymidine 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 2 and have already been tested with other people.
Current treatment has largely stabilized the disease course and improved disability scores. Although there is no cure for these mitochondrial disorders, it is important for patients to receive treatment when possible.
Different diseases fall into this category of mitochondrial encephalomyopathies. Mitochondrial encephalopathy is commonly associated to lactic breath, eye movement, or other neurological abnormalities. Mitochondrial encephalomyopathies can be further classified into a number of different disease syndromes. Mitochondrial diseases are generally inherited recessive.
Based on these data, in the United States approximately 2/100,000 people a year are newly diagnosed with MELAS, and MELA. One of the goals in the MELAS Foundation is to make an MELAS clinical diagnosis readily available to U.S. teenagers without compromising their access to other medical care.
Mitochondrial encephalomyopathies can present with symptoms including cognitive and behavioral changes, headaches, blurred vision, vomiting, or muscle weakness. An abnormal signal on electroencephalography or a rise in the level of creatine kinase in serum or urine may indicate mitochondrial encephalomyopathy.\n
This review suggests that there are a variety of causes for multiple encephalomyopathies; a possible common root cause involves mitochondrial dysfunction, and this review suggests that a unifying cause must be sought for all encephalomyopathies.
There are a number of treatments discussed in MEO, but only a few are commonly used, particularly in the context of MEO, such as high-protein, low-carbohydrate diets, and the use of high-dose oral glucose. There is an urgent need for new treatment options. For some of the treatment details discussed herein, more recent research evidence is currently lacking, whereas the others are well established.
Mitochondrial DNA mutations are the main cause of mitochondrial encephalomyopathies, but nuclear mutations are found in about 30% of patients with multiple system atrophy and leukoencephalopathy. The clinical presentation of mitochondrial encephalomyopathies varies widely, but the disease has an insidious clinical course. The treatment of mitochondrial and nuclear encephalomyopathies remains inadequate. The clinical course of multiple system atrophy is variable. There is no known cure for mitochondrial or nuclear encephalomyopathies.
New insights into the mechanisms of action of DCTP and DTT will help clarify the role of these agents in the treatment and the prognosis of myelodysplastic syndromes and other disorders characterized by defective nuclear energy production. The development of new chemotherapy agents, such as the inhibitors of thymidylate biosynthesis, which represent a new treatment approach for cancers and leukemia, is still under investigation.
We have identified only 9 new therapies. Most of these therapies are under development and await clinical assessment. They may be in use in the future.
Cytidine and thymidine are chemically similar in that they both contain a pyrimidine base (carbons 7 and 8 in the diagram) and have the same hydrogen atoms of the two rings adjacent to one another (at the carbons 1 and 5). The cytotoxic properties of nucleosides involve blocking the enzymatic activity of DNA polymerase. Deoxycytidine and deoxythymidine work by deactivating DNA polymerase to prevent DNA replication. Deoxycytidine interacts with the pyridine subunit, and deoxythymidine blocks deoxycytidine interaction on pyridine subunit. In contrast, in thymidine, the 2-carbon group replaces the methyl group.
The average age of onset for the mitochondrial encephalomyopathies is in early childhood and early adulthood, with a relatively stable age of onset over a lifetime. This suggests that, the mitochondrial disorder is a spectrum of disorders and there may be an age of onset that is different across different disorders.
These two nucleoside analogues have very similar toxicities. Among their common toxicities, oral administration of deoxycytidine may cause nausea and vomiting, diarrhoea, abdominal pain, and leukopenia. Deoxythymidine should be used with caution, and the infusion rate should be decreased in patients receiving this treatment.