Finding A Cure for Mitochondrial Diseases
Putative Cures being Researched
Putative methods of going about curing mitochondrial disease include (there are more interesting methods than what follows, check back here soon): 1) expression of transgenic wild-type mitochondrial proteins via modified mtDNA, 2) inhibition of mutant mtDNA replication, and 3) allotopic expression of mtDNA-encoded proteins (Aubrey de Grey).
The first method involves getting normal, wildtype DNA molecules into mitochondria and then having these newly-functional mitochondria proliferate to restore cellular energy production. The double-membrane of the mitochondrion makes getting the large wild-type DNA inside no small task by any means. Attaching DNA to proteins marked for import into the mitochondria is one pathway for this type of treatment. This has purportedly been successfully accomplished by scientists in cell culture (Khan and Bennett) and will hopefully prove efficacious with mammals in vivo.
The second method of putative treatment involves selectively inhibiting the replication of mutant mtDNA. If a known mutation causes a disease in a patient, then this mutation could be targeted as a binding site for molecules that inhibit replication machinery. If enough wildtype mitochondria exist in heteroplamsy with the mutant disease-causing mitochondria, then it is possibly that the selective suppression of mutant mitochondria might allow the wildtype mtDNA to take over and restore energy production for the patient.
The third method is perhaps the most audacious, and yet simultaneously what could be the most effacacious, in treating mitochondrial disease; "allotopic expression" here implies moving all of the proteins encoded by the mitochondrion into the nucleus. Not only will the codons have to be altered from the unique mitochondrial genetic code, but any of the resulting proteins in the nucleus will have to be targeted to the mitochondria. Headway is being made in this area, but still only low efficiencies in vitro studies have yet been acheived.
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