Skip to main content
SpringerLink
Log in

Emerging aspects of treatment in mitochondrial disorders

  • SSIEM 2014
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Mitochondrial diseases are clinically, biochemically and genetically heterogeneous disorders of two genomes, for which effective curative therapies are currently lacking. With the exception of a few rare vitamin/cofactor responsive conditions (including ACAD9 deficiency, disorders of coenzyme Q10 biosynthesis, and Leigh syndrome caused by mutations in the SLC19A3 transporter), the mainstay of treatment for the vast majority of patients involves supportive measures. The search for a cure for mitochondrial disease is the subject of intensive research efforts by many investigators across the globe, but the goal remains elusive. The clinical and genetic heterogeneity, multisystemic nature of many of these disorders, unpredictable natural course, relative inaccessibility of the mitochondrion and lack of validated, clinically meaningful outcome measures, have all presented great challenges to the design of rigorous clinical trials. This review discusses barriers to developing effective therapies for mitochondrial disease, models for evaluating the efficacy of novel treatments and summarises the most promising emerging therapies in six key areas: 1) antioxidant approaches; 2) stimulating mitochondrial biogenesis; 3) targeting mitochondrial membrane lipids, dynamics and mitophagy; 4) replacement therapy; 5) cell-based therapies; and 6) gene therapy approaches for both mtDNA and nuclear-encoded defects of mitochondrial metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahmad T, Mukherjee S, Pattnaik B et al (2014) Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. EMBO J 33:994–1010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ahola-Erkkila S, Carroll CJ, Peltola-Mjosund K et al (2010) Ketogenic diet slows down mitochondrial myopathy progression in mice. Hum Mol Genet 19:1974–1984

    Article  CAS  PubMed  Google Scholar 

  • Amato P, Tachibana M, Sparman M, Mitalipov S (2014) Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril 101:31–35

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bacman SR, Williams SL, Pinto M, Peralta S, Moraes CT (2013) Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat Med 19:1111–1113

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bax BE, Bain MD, Scarpelli M, Filosto M, Tonin P, Moran N (2013) Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement. Neurology 81:1269–1271

    Article  PubMed Central  PubMed  Google Scholar 

  • Blanchet L, Smeitink JA, van Emst-de Vries SE et al (2015) Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning. Sci Rep 5:8035. doi:10.1038/srep08035

  • Boczonadi V, Bansagi B, Horvath R (2014) Reversible infantile mitochondrial diseases. J Inherit Metab Dis

  • Bredenoord AL, Dondorp W, Pennings G, de Wert G (2011) Ethics of modifying the mitochondrial genome. J Med Ethics 37:97–100

    Article  CAS  PubMed  Google Scholar 

  • Broomfield A, Sweeney MG, Woodward CE et al (2014) Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease. J Inherit Metab Dis. doi:10.1007/s10545-014-9778-4

  • Camara Y, Gonzalez-Vioque E, Scarpelli M, Torres-Torronteras J, Marti R (2013) Feeding the deoxyribonucleoside salvage pathway to rescue mitochondrial DNA. Drug Discov Today 18:950–957

    Article  CAS  PubMed  Google Scholar 

  • Camara Y, Gonzalez-Vioque E, Scarpelli M et al (2014) Administration of deoxyribonucleosides or inhibition of their catabolism as a pharmacological approach for mitochondrial DNA depletion syndrome. Hum Mol Genet 23:2459–2467

    Article  CAS  PubMed  Google Scholar 

  • Cerutti R, Pirinen E, Lamperti C et al (2014) NAD(+)-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease. Cell Metab 19:1042–1049

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chadderton N, Palfi A, Millington-Ward S et al (2013) Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy. Eur J Hum Genet 21:62–68

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chang JC, Liu KH, Li YC et al (2013) Functional recovery of human cells harbouring the mitochondrial DNA mutation MERRF A8344G via peptide-mediated mitochondrial delivery. Neurosignals 21:160–173

    Article  CAS  PubMed  Google Scholar 

  • Craven L, Tuppen HA, Greggains GD et al (2010) Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 465:82–85

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dassa EP, Dufour E, Goncalves S et al (2009) Expression of the alternative oxidase complements cytochrome c oxidase deficiency in human cells. EMBO Mol Med 1:30–36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • De Paepe B, Vandemeulebroecke K, Smet J et al (2014) Effect of resveratrol on cultured skin fibroblasts from patients with oxidative phosphorylation defects. Phytother Res 28:312–316

    Article  Google Scholar 

  • Di Meo I, Auricchio A, Lamperti C, Burlina A, Viscomi C, Zeviani M (2012) Effective AAV-mediated gene therapy in a mouse model of ethylmalonic encephalopathy. EMBO Mol Med 4:1008–1014

    Article  PubMed Central  PubMed  Google Scholar 

  • Distelmaier F, Visch HJ, Smeitink JA, Mayatepek E, Koopman WJ, Willems PH (2009) The antioxidant Trolox restores mitochondrial membrane potential and Ca2+ −stimulated ATP production in human complex I deficiency. J Mol Med (Berl) 87:515–522

    Article  CAS  Google Scholar 

  • Doudna JA, Charpentier E (2014) Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346:1258096. doi:10.1126/science.1258096

  • El-Khoury R, Dufour E, Rak M et al (2013) Alternative oxidase expression in the mouse enables bypassing cytochrome c oxidase blockade and limits mitochondrial ROS overproduction. PLoS Genet 9:e1003182. doi:10.1371/journal.pgen.1003182

  • El-Khoury R, Kemppainen KK, Dufour E, Szibor M, Jacobs HT, Rustin P (2014) Engineering the alternative oxidase gene to better understand and counteract mitochondrial defects: state of the art and perspectives. Br J Pharmacol 171:2243–2249

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ellouze S, Augustin S, Bouaita A et al (2008) Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. Am J Hum Genet 83:373–387

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Enns GM, Kinsman SL, Perlman SL et al (2012) Initial experience in the treatment of inherited mitochondrial disease with EPI-743. Mol Genet Metab 105:91–102

    Article  CAS  PubMed  Google Scholar 

  • Falk MJ, Shen L, Gonzalez M et al (2015) Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities. Mol Genet Metab 114:388–396

    Article  CAS  PubMed  Google Scholar 

  • Fassone E, Wedatilake Y, Devile CJ, Chong WK, Carr LJ, Rahman S (2013) Treatable Leigh-like encephalopathy presenting in adolescence. BMJ Case Rep 2013:200838. doi:10.1136/bcr-2013-200838

  • Foley AR, Menezes MP, Pandraud A et al (2014) Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 137:44–56

    Article  PubMed Central  PubMed  Google Scholar 

  • Francisci S, Montanari A, De LC, Frontali L (2011) Peptides from aminoacyl-tRNA synthetases can cure the defects due to mutations in mt tRNA genes. Mitochondrion 11:919–923

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gagne KE, Ghazvinian R, Yuan D et al (2014) Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia. Blood 124:437–440

    Article  CAS  PubMed  Google Scholar 

  • Gammage PA, Rorbach J, Vincent AI, Rebar EJ, Minczuk M (2014) Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. EMBO Mol Med 6:458–466

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gerards M, van den Bosch BJ, Danhauser K et al (2011) Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene. Brain 134:210–219

    Article  PubMed  Google Scholar 

  • Golubitzky A, Dan P, Weissman S, Link G, Wikstrom JD, Saada A (2011) Screening for active small molecules in mitochondrial complex I deficient patient’s fibroblasts, reveals AICAR as the most beneficial compound. PLoS One 6:e26883. doi:10.1371/journal.pone.0026883

  • Green DR, Van Houten B (2011) SnapShot: mitochondrial quality control. Cell 147(950):950. doi:10.1016/j.cell.2011.10.036

  • Guy J, Qi X, Koilkonda RD et al (2009) Efficiency and safety of AAV-mediated gene delivery of the human ND4 complex I subunit in the mouse visual system. Invest Ophthalmol Vis Sci 50:4205–4214

    Article  PubMed Central  PubMed  Google Scholar 

  • Haack TB, Klee D, Strom TM et al (2014) Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. Brain 137, e295. doi:10.1093/brain/awu128

  • Hakkaart GA, Dassa EP, Jacobs HT, Rustin P (2006) Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration. EMBO Rep 7:341–345

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Halter J, Schupbach WM, Casali C et al (2011) Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant 46:330–337

    Article  CAS  PubMed  Google Scholar 

  • Hargreaves IP, Sheena Y, Land JM, Heales SJ (2005) Glutathione deficiency in patients with mitochondrial disease: implications for pathogenesis and treatment. J Inherit Metab Dis 28:81–88

    Article  CAS  PubMed  Google Scholar 

  • Hirano M, Marti R, Casali C et al (2006) Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. Neurology 67:1458–1460

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hornig-Do HT, Montanari A, Rozanska A et al (2014) Human mitochondrial leucyl tRNA synthetase can suppress non cognate pathogenic mt-tRNA mutations. EMBO Mol Med 6:183–193

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hughes SD, Kanabus M, Anderson G et al (2014) The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells. J Neurochem 129:426–433

    Article  CAS  PubMed  Google Scholar 

  • Islam MN, Das SR, Emin MT et al (2012) Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med 18:759–765

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jacobson J, Duchen MR, Hothersall J, Clark JB, Heales SJ (2005) Induction of mitochondrial oxidative stress in astrocytes by nitric oxide precedes disruption of energy metabolism. J Neurochem 95:388–395

    Article  CAS  PubMed  Google Scholar 

  • Johnson SC, Yanos ME, Kayser EB et al (2013) mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science 342:1524–1528

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kanabus M, Heales SJ, Rahman S (2014) Development of pharmacological strategies for mitochondrial disorders. Br J Pharmacol 171:1798–1817

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaufmann P, Engelstad K, Wei Y et al (2011) Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology 77:1965–1971

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kawamura E, Yamada Y, Harashima H (2013) Mitochondrial targeting functional peptides as potential devices for the mitochondrial delivery of a DF-MITO-porter. Mitochondrion 13:610–614

    Article  CAS  PubMed  Google Scholar 

  • Kerr DS (2013) Review of clinical trials for mitochondrial disorders: 1997–2012. Neurotherapeutics 10:307–319

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Khan NA, Auranen M, Paetau I et al (2014) Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. EMBO Mol Med 6:721–731

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klopstock T, Yu-Wai-Man P, Dimitriadis K et al (2011) A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain 134:2677–2686

    Article  PubMed Central  PubMed  Google Scholar 

  • Lemonde H, Rahman S (2015) Inherited mitochondrial disease. Paediatr Child Health 25(3):133–138. doi:10.1016/j.paed.2014.11.002

  • Libri V, Brown AP, Gambarota G et al (2012) A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers. PLoS One 7:e51395. doi:10.1371/journal.pone.0051395

  • Lightowlers RN, Chrzanowska-Lightowlers ZM (2014) Salvaging hope: is increasing NAD(+) a key to treating mitochondrial myopathy? EMBO Mol Med 6:705–707

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu CS, Chang JC, Kuo SJ et al (2014) Delivering healthy mitochondria for the therapy of mitochondrial diseases and beyond. Int J Biochem Cell Biol 53:141–146

    Article  CAS  PubMed  Google Scholar 

  • Lopes CA, Le BC, Mathieu L et al (2014) Beneficial effects of resveratrol on respiratory chain defects in patients’ fibroblasts involve estrogen receptor and estrogen-related receptor alpha signaling. Hum Mol Genet 23:2106–2119

    Article  Google Scholar 

  • Mak AN, Bradley P, Cernadas RA, Bogdanove AJ, Stoddard BL (2012) The crystal structure of TAL effector PthXo1 bound to its DNA target. Science 335:716–719

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Manfredi G, Fu J, Ojaimi J et al (2002) Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. Nat Genet 30:394–399

    Article  CAS  PubMed  Google Scholar 

  • Martinelli D, Catteruccia M, Piemonte F et al (2012) EPI-743 reverses the progression of the pediatric mitochondrial disease–genetically defined Leigh Syndrome. Mol Genet Metab 107:383–388

    Article  CAS  PubMed  Google Scholar 

  • Minczuk M, Papworth MA, Miller JC, Murphy MP, Klug A (2008) Development of a single-chain, quasi-dimeric zinc-finger nuclease for the selective degradation of mutated human mitochondrial DNA. Nucleic Acids Res 36:3926–3938

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Montini G, Malaventura C, Salviati L (2008) Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency. N Engl J Med 358:2849–2850

    Article  CAS  PubMed  Google Scholar 

  • Moran NF, Bain MD, Muqit MM, Bax BE (2008) Carrier erythrocyte entrapped thymidine phosphorylase therapy for MNGIE. Neurology 71:686–688

    Article  CAS  PubMed  Google Scholar 

  • Murphy JL, Blakely EL, Schaefer AM et al (2008) Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain 131:2832–2840

    Article  PubMed  Google Scholar 

  • Nesbitt V, Pitceathly RD, Turnbull DM et al (2013) The UK MRC mitochondrial disease patient cohort study: clinical phenotypes associated with the m.3243A>G mutation-implications for diagnosis and management. J Neurol Neurosurg Psychiatry 84:936–938

  • Orngreen MC, Madsen KL, Preisler N, Andersen G, Vissing J, Laforet P (2014) Bezafibrate in skeletal muscle fatty acid oxidation disorders: a randomized clinical trial. Neurology 82:607–613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Park H, Davidson E, King MP (2008) Overexpressed mitochondrial leucyl-tRNA synthetase suppresses the A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. RNA 14:2407–2416

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Perez-Duenas B, Serrano M, Rebollo M et al (2013) Reversible lactic acidosis in a newborn with thiamine transporter-2 deficiency. Pediatrics 131:e1670–e1675

    Article  PubMed  Google Scholar 

  • Perli E, Giordano C, Tuppen HA et al (2012) Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic m.4277T>C mitochondrial tRNA(Ile) mutation causing hypertrophic cardiomyopathy. Hum Mol Genet 21:85–100

    Article  PubMed  Google Scholar 

  • Perli E, Giordano C, Pisano A et al (2014) The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells. EMBO Mol Med 6:169–182

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pfeffer G, Majamaa K, Turnbull DM, Thorburn D, Chinnery PF (2012) Treatment for mitochondrial disorders. Cochrane Database Syst Rev 4, CD004426. doi:10.1002/14651858

  • Qi X, Qvit N, Su YC, Mochly-Rosen D (2013) A novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity. J Cell Sci 126:789–802

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rahman S (2012) Mitochondrial disease and epilepsy. Dev Med Child Neurol 54:397–406

    Article  PubMed  Google Scholar 

  • Rahman S, Hanna MG (2009) Diagnosis and therapy in neuromuscular disorders: diagnosis and new treatments in mitochondrial diseases. J Neurol Neurosurg Psychiatry 80:943–953

    Article  CAS  PubMed  Google Scholar 

  • Rahman S, Poulton J (2009) Diagnosis of mitochondrial DNA depletion syndromes. Arch Dis Child 94:3–5

    Article  PubMed  Google Scholar 

  • Rahman S, Clarke CF, Hirano M (2012) 176th ENMC international workshop: diagnosis and treatment of coenzyme Q(10) deficiency. Neuromuscul Disord 22:76–86

    Article  PubMed Central  PubMed  Google Scholar 

  • Reinhardt K, Dowling DK, Morrow EH (2013) Medicine. Mitochondrial replacement, evolution, and the clinic. Science 341:1345–1346

    Article  PubMed  Google Scholar 

  • Rinaldi T, Lande R, Bolotin-Fukuhara M, Frontali L (1997) Additional copies of the mitochondrial Ef-Tu and aspartyl-tRNA synthetase genes can compensate for a mutation affecting the maturation of the mitochondrial tRNAAsp. Curr Genet 31:494–496

    Article  CAS  PubMed  Google Scholar 

  • Sadun AA, Chicani CF, Ross-Cisneros FN et al (2012) Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy. Arch Neurol 69:331–338

    Article  PubMed  Google Scholar 

  • Sallevelt SC, Dreesen JC, Drusedau M et al (2013) Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success. J Med Genet 50:125–132

    Article  CAS  PubMed  Google Scholar 

  • Salmi H, Leonard JV, Rahman S, Lapatto R (2012) Plasma thiol status is altered in children with mitochondrial diseases. Scand J Clin Lab Invest 72(2):152–157. doi:10.3109/00365513.2011.646299

  • Santra S, Gilkerson RW, Davidson M, Schon EA (2004) Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann Neurol 56:662–669

    Article  CAS  PubMed  Google Scholar 

  • Shi H, Gao J, Pei H et al (2012) Adeno-associated virus-mediated gene delivery of the human ND4 complex I subunit in rabbit eyes. Clin Experiment Ophthalmol 40:888–894

    Article  PubMed  Google Scholar 

  • Sofou K, de Coo IF, Isohanni P et al (2014) A multicenter study on Leigh syndrome: disease course and predictors of survival. Orphanet J Rare Dis 9:52. doi:10.1186/1750-1172-9-52

  • Spees JL, Olson SD, Whitney MJ, Prockop DJ (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A 103:1283–1288

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tachibana M, Sparman M, Sritanaudomchai H et al (2009) Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature 461:367–372

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tachibana M, Amato P, Sparman M et al (2013) Towards germline gene therapy of inherited mitochondrial diseases. Nature 493:627–631

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Taivassalo T, Haller RG (2005) Exercise and training in mitochondrial myopathies. Med Sci Sports Exerc 37:2094–2101

    Article  CAS  PubMed  Google Scholar 

  • Taivassalo T, Gardner JL, Taylor RW et al (2006) Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions. Brain 129:3391–3401

    Article  PubMed  Google Scholar 

  • Tanaka M, Borgeld HJ, Zhang J et al (2002) Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J Biomed Sci 9:534–541

    CAS  PubMed  Google Scholar 

  • Thorburn DR (2004) Mitochondrial disorders: prevalence, myths and advances. J Inherit Metab Dis 27:349–362

    Article  CAS  PubMed  Google Scholar 

  • Torres-Torronteras J, Gomez A, Eixarch H et al (2011) Hematopoietic gene therapy restores thymidine phosphorylase activity in a cell culture and a murine model of MNGIE. Gene Ther 18:795–806

    Article  CAS  PubMed  Google Scholar 

  • Treff NR, Campos J, Tao X, Levy B, Ferry KM, Scott RT Jr (2012) Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder. Fertil Steril 98:1236–1240

    Article  CAS  PubMed  Google Scholar 

  • Tumino M, Meli C, Farruggia P et al (2011) Clinical manifestations and management of four children with Pearson syndrome. Am J Med Genet A 155A:3063–3066

    Article  PubMed  Google Scholar 

  • Viscomi C, Burlina AB, Dweikat I et al (2010) Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy. Nat Med 16:869–871

    Article  CAS  PubMed  Google Scholar 

  • Viscomi C, Bottani E, Civiletto G et al (2011) In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis. Cell Metab 14:80–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wedatilake Y, Brown R, McFarland R et al (2013) SURF1 deficiency: a multi-centre natural history study. Orphanet J Rare Dis 8:96. doi:10.1186/1750-1172-8-96

  • Wenz T, Diaz F, Spiegelman BM, Moraes CT (2008) Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab 8:249–256

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yatsuga S, Suomalainen A (2012) Effect of bezafibrate treatment on late-onset mitochondrial myopathy in mice. Hum Mol Genet 21:526–535

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

SR is supported by Great Ormond Street Hospital Children’s Charity and currently receives research grant funding from The Wellcome Trust, The Lily Foundation, and Vitaflo International Ltd.

Compliance with Ethics Guidelines

ᅟ

Conflict of interest

Professor Rahman declares that she has received grant support from Vitaflo International Ltd, but the funder played no role in the preparation of this manuscript.

Animal rights

This article is a review, and does not contain any studies with human or animal subjects performed by the author.

Author contribution

Professor Rahman is the sole author of this manuscript.

Author information

Authors and Affiliations

  1. Mitochondrial Research Group, Genetics and Genomic Medicine, Institute of Child Health, University College London and Metabolic Unit, Great Ormond Street Hospital, 30 Guilford Street, London, WC1N 1EH, UK

    Shamima Rahman

Authors
  1. Shamima Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shamima Rahman.

Additional information

Communicated by: Eva Morava

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rahman, S. Emerging aspects of treatment in mitochondrial disorders. J Inherit Metab Dis 38, 641–653 (2015). https://doi.org/10.1007/s10545-015-9855-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-015-9855-3

Keywords

Search

Navigation