NEW DIRECTIONS IN MITOCHONDRIAL DISORDERS
Defects in the energy-producing units of cells known as mitochondria have been known for some years to cause a wide range of disorders known as mitochondrial myopathies or mitochondrial encephalomyopathies. Mitochondria have their own DNA and are also influenced by DNA in the cell's nucleus, so defects in either type of DNA can affect their vital functions.
Understanding of such disorders was scant until recently. Now, MDA grantees Salvatore DiMauro and Eric Schon, both of the Neurology Department at New York's Columbia University, have worked out many of the steps involved in these disorders and have some ideas on how they might be treated. Their report is in the January issue of The Neuroscientist.
Correcting flaws in mitochondrial DNA in laboratory dishes can be done by blocking abnormal DNA with so-called peptide nucleic acids, DiMauro says. He notes that adding a protein to mitochondria when there's one missing or defective can be done by adding a gene for that protein to the cell's nucleus, after changing the gene slightly so that it tells the cell to produce a mitochondrial protein. This too has been accomplished in the lab. DiMauro emphasizes, however, that both strategies depend on first getting the peptide nucleic acid or the new gene into the affected tissue, not a problem in a lab dish but a major hurdle when the target tissue is nerve or muscle inside the body.
Mitochondrial disorders are now sometimes treated with substances that seem to compensate for the loss of some energy production functions. These substances include coenzyme Q10, carnitine, vitamins C and K, and various components of the vitamin B complex, especially riboflavin.
Even a little help can mean a lot in mitochondrial disorders, says DiMauro, a neurologist. "Patients can be sick when they have 85 percent mutant mitochondria in a given tissue, but if they have 80 percent, they may be much, much better and may not show symptoms. So, if you can change the proportions even slightly, you may do the patient a lot of good."
Schon, a molecular biologist, is working on developing the first animal models of mitochondrial encephalomyopathies, in which treatment strategies can be tested.
-end-
You may be interested in other mitochondrial disorder information and research on this site:
|
