Strategies for treating disorders of the mitochondrial genome.
Defects of the mitochondrial genome are a significant cause of disease. Patients suffer from a wide variety of clinical presentations, ranging from fatal infantile disease to mild muscle weakness. Most disorders, however, are characterized by inexorable progression. As mutations often cause defects in several components of the complexes that couple oxidative phosphorylation, this terminal state of oxidative metabolism cannot be readily bypassed by dietary means, leading to the search for novel therapies. In this article, we present the theory behind several concepts and report progress. We also discuss some of the recent difficulties encountered in the progress towards an antigenomc approach to treating mtDNA disorders.
Smith
Paul M
PM
Mitochondrial Research Group, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Ross
Günther F
GF
Taylor
Robert W
RW
Turnbull
Douglass M
DM
Lightowlers
Robert N
RN
D001692:Biological Transport; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D015894:Genome, Human; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000628:therapy*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012343:RNA, Transfer