Initial experience in the treatment of inherited mitochondrial disease with EPI-743

Molecular Genetics and Metabolism

Volumn 105, Issue 1, 2012, Pages 91-102

  Enns, Gregory M ^a   Kinsman, Stephen L ^b   Perlman, Susan L ^c   Spicer, Kenneth M ^b   Abdenur, Jose E ^d   Cohen, Bruce H ^e   Amagata, Akiko ^f   Barnes, Adam ^f   Kheifets, Viktoria ^f   Shrader, William D ^f   Thoolen, Martin ^f   Blankenberg, Francis ^a   Miller, Guy ^f,g  

^a LUCILE PACKARD CHILDREN S HOSPITAL   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d CHILDREN S HOSPITAL OF ORANGE COUNTY   (United States)

^e AKRON CHILDREN'S HOSPITAL   (United States)

^f BioElectron Technology Corporation   (United States)

^g STANFORD UNIVERSITY   (United States)

Author keywords

Tocotrienol quinone; Friedreich ataxia; Leigh syndrome; MELAS; Mitochondrial DNA deletion syndrome; Polymerase deficiency

Indexed keywords

1,4 BENZOQUINONE DERIVATIVE; DNA DIRECTED DNA POLYMERASE GAMMA; EPI 743; HEXAMETHYLPROPYLENE AMINE OXIME TECHNETIUM TC 99M; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CHILD; CHOREOATHETOSIS; CLINICAL ARTICLE; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; FEMALE; GASTROENTERITIS; GASTROINTESTINAL MOTILITY DISORDER; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; MORTALITY; MYOCLONUS; PANCREATITIS; PNEUMONIA; PRESCHOOL CHILD; PRIORITY JOURNAL; QUALITY OF LIFE; RELAPSE; RISK FACTOR; SCHOOL CHILD; SCORING SYSTEM; SEIZURE; SIDE EFFECT; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; STROKE; SURVIVAL RATE; TERMINAL CARE; TREATMENT RESPONSE; URINARY TRACT INFECTION;

ADOLESCENT; ADULT; BENZOQUINONES; BRAIN; CELLS, CULTURED; CHILD; CHILD, PRESCHOOL; FEMALE; FIBROBLASTS; GENE EXPRESSION REGULATION; GENETIC DISEASES, INBORN; HUMANS; MALE; MITOCHONDRIAL DISEASES; OXIDATIVE STRESS; OXIMES; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON; UBIQUINONE;

EID: 84855355930     PISSN: 10967192     EISSN: 10967206     Source Type: Journal    
DOI: 10.1016/j.ymgme.2011.10.009     Document Type: Article

References (44)

1. DiMauro S., Schon E.A. Mitochondrial respiratory-chain diseases. N. Engl. J. Med. 2003, 348:2656-2668.
2. Spinazzola A., Zeviani M. Mitochondrial diseases: a cross-talk between mitochondrial and nuclear genomes. Adv. Exp. Med. Biol. 2009, 652:69-84.
3. Elliott H.R., Samuels D.C., Eden J.A., Relton C.L., Chinnery P.F. Pathogenic mitochondrial DNA mutations are common in the general population. Am. J. Hum. Genet. 2008, 83:254-260.
4. Kerr D.S. Treatment of mitochondrial electron transport chain disorders: a review of clinical trials over the past decade. Mol. Genet. Metab. 2010, 99:246-255.
5. Wallace D.C. Mitochondrial diseases in man and mouse. Science 1999, 283:1482-1488.
6. Atkuri K.R., Cowan T.M., Kwan T., Ng A., Herzenberg L.A., Enns G.M. Inherited disorders affecting mitochondrial function are associated with glutathione deficiency and hypocitrullinemia. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:3941-3945.
7. Hargreaves I.P., Sheena Y., Land J.M., Heales S.J. Glutathione deficiency in patients with mitochondrial disease: implications for pathogenesis and treatment. J. Inherit. Metab. Dis. 2005, 28:81-88.
8. Tarnopolsky M.A. The mitochondrial cocktail: rationale for combined nutraceutical therapy in mitochondrial cytopathies. Adv. Drug Deliv. Rev. 2008, 60:1561-1567.
9. Matthews R.T., Yang L., Browne S., Baik M., Beal M.F. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:8892-8897.
10. Shults C.W., Haas R. Clinical trials of coenzyme Q10 in neurological disorders. Biofactors 2005, 25:117-126.
11. Glover E.I., Martin J., Maher A., Thornhill R.E., Moran G.R., Tarnopolsky M.A. A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle Nerve 2010, 42:739-748.
12. Stamelou M., Reuss A., Pilatus U., Magerkurth J., Niklowitz P., Eggert K.M., Krisp A., Menke T., Schade-Brittinger C., Oertel W.H., Hoglinger G.U. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial. Mov. Disord. 2008, 23:942-949.
13. Chen R.S., Huang C.C., Chu N.S. Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study. Eur. Neurol. 1997, 37:212-218.
14. Ikejiri Y., Mori E., Ishii K., Nishimoto K., Yasuda M., Sasaki M. Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS. Neurology 1996, 47:583-585.
15. Mashima Y., Hiida Y., Oguchi Y. Remission of Leber's hereditary optic neuropathy with idebenone. Lancet 1992, 340:368-369.
16. Klopstock T., Yu-Wai-Man P., Dimitriadis K., Rouleau J., Heck S., Bailie M., Atawan A., Chattopadhyay S., Schubert M., Garip A., Kernt M., Petraki D., Rummey C., Leinonen M., Metz G., Griffiths P.G., Meier T., Chinnery P.F. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain 2011, 134:2677-2686.
17. Drinkard B.E., Keyser R.E., Paul S.M., Arena R., Plehn J.F., Yanovski J.A., Di Prospero N.A. Exercise capacity and idebenone intervention in children and adolescents with Friedreich ataxia. Arch. Phys. Med. Rehabil. 2010, 91:1044-1050.
18. Lynch D.R., Perlman S.L., Meier T. A phase 3, double-blind, placebo-controlled trial of idebenone in Friedreich ataxia. Arch. Neurol. 2010, 67:941-947.
19. Esposti M.D., Ngo A., Ghelli A., Benelli B., Carelli V., McLennan H., Linnane A.W. The interaction of Q analogs, particularly hydroxydecyl benzoquinone (idebenone), with the respiratory complexes of heart mitochondria. Arch. Biochem. Biophys. 1996, 330:395-400.
20. Shrader W.D., Amagata A., Barnes A., Enns G.M., Hinman A., Jankowski O., Kheifets V., Komatsuzaki R., Lee E., Mollard P., Murase K., Sadun A.A., Thoolen M., Wesson K., Miller G. alpha-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging. Bioorg. Med. Chem. Lett. 2011, 21:3693-3698.
21. Jacquier-Sarlin M.R., Polla B.S., Slosman D.O. Oxido-reductive state: the major determinant for cellular retention of technetium-99m-HMPAO. J. Nucl. Med. 1996, 37:1413-1416.
22. Phoenix C., Schaefer A.M., Elson J.L., Morava E., Bugiani M., Uziel G., Smeitink J.A., Turnbull D.M., McFarland R. A scale to monitor progression and treatment of mitochondrial disease in children. Neuromuscul. Disord. 2006, 16:814-820.
23. Schaefer A.M., Phoenix C., Elson J.L., McFarland R., Chinnery P.F., Turnbull D.M. Mitochondrial disease in adults: a scale to monitor progression and treatment. Neurology 2006, 66:1932-1934.
24. Sasaki T., Senda M. Technetium-99m-meso-HMPAO as a potential agent to image cerebral glutathione content. J. Nucl. Med. 1997, 38:1125-1129.
25. Colloby S.J., Fenwick J.D., Williams E.D., Paling S.M., Lobotesis K., Ballard C., McKeith I., O'Brien J.T. A comparison of (99m)Tc-HMPAO SPET changes in dementia with Lewy bodies and Alzheimer's disease using statistical parametric mapping. Eur. J. Nucl. Med. Mol. Imaging 2002, 29:615-622.
26. Talairach J., Tournoux P. Co-planar Sterotaxic Atlas of the Human Brain: 3-Dimensional Proportional System-An Approach to Cerebral Imaging 1988, Thieme Medical Publishers, New York.
27. Suess E., Malessa S., Ungersbock K., Kitz P., Podreka I., Heimberger K., Hornykiewicz O., Deecke L. Technetium-99m-d,1-hexamethylpropyleneamine oxime (HMPAO) uptake and glutathione content in brain tumors. J. Nucl. Med. 1991, 32:1675-1681.
28. Zerarka S., Pellerin L., Slosman D., Magistretti P.J. Astrocytes as a predominant cellular site of (99m)Tc-HMPAO retention. J. Cereb. Blood Flow Metab. 2001, 21:456-468.
29. Chan S.S., Copeland W.C. DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations. Biochim. Biophys. Acta 2009, 1787:312-319.
30. Volkert W.A., Hoffman T.J., Seger R.M., Troutner D.E., Holmes R.A. 99mTc-propylene amine oxime (99mTc-PnAO); a potential brain radiopharmaceutical. Eur. J. Nucl. Med. 1984, 9:511-516.
31. Neirinckx R.D., Canning L.R., Piper I.M., Nowotnik D.P., Pickett R.D., Holmes R.A., Volkert W.A., Forster A.M., Weisner P.S., Marriott J.A., et al. Technetium-99m d, l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion. J. Nucl. Med. 1987, 28:191-202.
32. Kamijo Y., Soma K., Kondo R., Ohwada T. Transient diffuse cerebral hypoperfusion in Tc-99m HMPAO SPECT of the brain during withdrawal syndrome following acute barbiturate poisoning. Vet. Hum. Toxicol. 2002, 44:348-350.
33. Haffner M.E., Whitley J., Moses M. Two decades of orphan product development. Nat. Rev. Drug Discov. 2002, 1:821-825.
34. Schaefer A.M., Taylor R.W., Turnbull D.M., Chinnery P.F. The epidemiology of mitochondrial disorders-past, present and future. Biochim. Biophys. Acta 2004, 1659:115-120.
35. Vockley J., Vockley C.M. Clinical trials: curing a critical deficiency in metabolic medicine. Mol. Genet. Metab. 2010, 99:244-245.
36. Heemstra H.E., van Weely S., Buller H.A., Leufkens H.G., de Vrueh R.L. Translation of rare disease research into orphan drug development: disease matters. Drug Discov. Today 2009, 14:1166-1173.
37. Martensson J., Lai J.C., Meister A. High-affinity transport of glutathione is part of a multicomponent system essential for mitochondrial function. Proc. Natl. Acad. Sci. U. S. A. 1990, 87:7185-7189.
38. Jain A., Martensson J., Stole E., Auld P.A., Meister A. Glutathione deficiency leads to mitochondrial damage in brain. Proc. Natl. Acad. Sci. U. S. A. 1991, 88:1913-1917.
39. Sian J., Dexter D.T., Lees A.J., Daniel S., Agid Y., Javoy-Agid F., Jenner P., Marsden C.D. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol. 1994, 36:348-355.
40. Heales S.J., Davies S.E., Bates T.E., Clark J.B. Depletion of brain glutathione is accompanied by impaired mitochondrial function and decreased N-acetyl aspartate concentration. Neurochem. Res. 1995, 20:31-38.
41. Barker J.E., Bolanos J.P., Land J.M., Clark J.B., Heales S.J. Glutathione protects astrocytes from peroxynitrite-mediated mitochondrial damage: implications for neuronal/astrocytic trafficking and neurodegeneration. Dev. Neurosci. 1996, 18:391-396.
42. Dringen R. Glutathione metabolism and oxidative stress in neurodegeneration. Eur. J. Biochem. 2000, 267:4903.
43. Heales S.J., Bolanos J.P. Impairment of brain mitochondrial function by reactive nitrogen species: the role of glutathione in dictating susceptibility. Neurochem. Int. 2002, 40:469-474.
44. Viscomi C., Burlina A.B., Dweikat I., Savoiardo M., Lamperti C., Hildebrandt T., Tiranti V., Zeviani M. Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy. Nat. Med. 2010, 16:869-871.