Pharmacotherapy for Friedreich Ataxia

CNS Drugs

Volumn 23, Issue 3, 2009, Pages 213-223

  Tsou, Amy Y ^a   Friedman, Lisa S ^a,b   Wilson, Robert B ^a   Lynch, David R ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOCOPHEROL; BACLOFEN; BML 20; DEFERIPRONE; DEFEROXAMINE; FRATAXIN; HISTONE DEACETYLASE INHIBITOR; IDEBENONE; MITOQUINONE; PLACEBO; RECOMBINANT ERYTHROPOIETIN; UBIDECARENONE; UNCLASSIFIED DRUG;

AGRANULOCYTOSIS; BRAIN FUNCTION; CLINICAL TRIAL; DIARRHEA; DIZZINESS; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MEGADOSE; FERRITIN BLOOD LEVEL; FRIEDREICH ATAXIA; GASTROINTESTINAL SYMPTOM; GUILLAIN BARRE SYNDROME; HEART VENTRICLE HYPERTROPHY; HEMOGLOBIN BLOOD LEVEL; HUMAN; IN VITRO STUDY; IRON BLOOD LEVEL; LOW DRUG DOSE; MITOCHONDRION; MONOTHERAPY; MUSCULOSKELETAL PAIN; NAUSEA; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SPASTICITY; SYMPTOM; VOMITING;

ANIMALS; ANTIOXIDANTS; ENZYME INHIBITORS; ERYTHROPOIETIN, RECOMBINANT; FRIEDREICH ATAXIA; HISTONE DEACETYLASES; HUMANS; IRON CHELATING AGENTS; ORGANOPHOSPHORUS COMPOUNDS; PYRIDONES; UBIQUINONE;

EID: 63149125653     PISSN: 11727047     EISSN: None     Source Type: Journal    
DOI: 10.2165/00023210-200923030-00003     Document Type: Review

References (76)

1. Babady NE, Carelle N, Wells RD, et al. Advancements in the pathophysiology of Friedreich's ataxia and new prospects for treatments. Molec Genet Metabolism 2007; 92: 23-35
2. Cooper JM, Schapira AH. Friedreich's ataxia: disease mechanisms, antioxidant and coenzyme Q10 therapy. BioFactors 2003; 18: 163-71
3. Harding AE. Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 1981; 104: 589-620
4. Lynch DR, Farmer JM, Balcer LJ, et al. Friedreich ataxia: effects of genetic understanding on clinical evaluation and therapy. Arch Neurol 2002; 59: 743-7
5. Pandolfo M. Molecular pathogenesis of Friedreich ataxia. Arch Neurol 1999; 56: 1201-8
6. Singh G, Binstadt BA, Black DF, et al. Electroconvulsive therapy and Friedreich's ataxia. J Electroconvuls Ther 2001; 17: 53-4
7. Bhidayasiri R, Perlman SL, Pulst SM, et al. Late-onset Friedreich ataxia: phenotypic analysis, magnetic resonance imaging findings, and review of the literature. Arch Neurol 2004; 62: 1865-9
8. Monrós E, Moltó MD, Martínez F, et al. Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat. Amer J Hum Genet 1997; 61: 101-10
9. Santoro L, De Michele G, Perretti A, et al. Relation between trinucleotide GAA repeat length and sensory neuropathy in Friedreich's ataxia. J Neurol Neurosurg Psych 1999; 66: 93-6
10. Ragno M, De Michele G, Cavalcanti F, et al. Broadened Friedreich's ataxia phenotype after gene cloning: minimal GAA expansion causes late-onset spastic ataxia. Neurology 1997; 49: 1617-20
11. Campuzano V, Montermini L, Moltò MD, et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271: 1423-7
12. Bidichandani SI, Ashizawa T, Patel PI. Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion. Amer J Human Genet 1997; 60: 1251-6
13. McCormack ML, Guttmann RP, Schumann M, et al. Frataxin point mutations in two patients with Friedreich's ataxia and unusual clinical features. J Neurol Neurosurg Psychiatry 2000; 68: 661-4
14. Cossée M, Dürr A, Schmitt M, et al. Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes. Ann Neurol 1999; 45: 200-6
15. Isaya G, O'Neill HA, Gakh O, et al. Functional studies of frataxin. Acta Paediatr 2004; 93 Suppl.: 68-71
16. Cavadini P, O'Neill HA, Benada O, et al. Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia. Hum Mol Genet 2002; 11: 217-27
17. Tan G, Chen LS, Lonnerdal B, et al. Frataxin expression rescues mitochondrial dysfunctions in FRDA cells. Hum Mol Genet 2001; 10: 2099-107
18. Wilson RB. Iron dysregulation in Friedreich ataxia. Semin Pediatr Neurol 2006; 13: 166-75
19. Martelli A, Wattenhofer-Donzé M, Schmucker S, et al. Non-mitochondrial proteins: frataxin is essential for extra-mitochondrial Fe-S cluster proteins in mammalian tissues. Hum Mol Genet 2007; 16 (22): 2651-8
20. Bulteau AL, O'Neill HA, Kennedy MC, et al. Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 2004; 305 (5681): 242-5
21. Chapela SP, Burgos HI, Salazar AI, et al. Biochemical study of idebenone effect on mitochondrial metabolism of yeast. Cell Biol Internat 2008 Jan; 32 (1): 146-50
22. McDaniel DH, Neudecker BA, Dinardo JC, et al. Idebenone, a new antioxidant: part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants. J Cosmetic Derm 2005; 4: 10-7
23. Rustin P. The use of antioxidants in Friedreich's ataxia treatment. Expert Opin Investig Drugs 2003; 12: 569-75
24. Idebenone: monograph. Altern Med Rev 2001; 6: 83-6
25. Rustin P, Munnich A, Rötig A. Quinone analogs prevent enzymes targeted in Friedreich ataxia from iron-induced injury in vitro. BioFactors 1999; 9: 247-51
26. Imada I, Fujita T, Sugiyama Y, et al. Effects of idebenone and related compounds on respiratory activities of brain mitochondria, and on lipid peroxidation of their membranes. Arch Gerontol Geriatr 1989; 8 (3): 323-41
27. Sugiyama Y, Fujita T, Matsumoto M, et al. Effects of idebenone (CV-2619) and its metabolites on respiratory activity and lipid peroxidation in brain mitochondria from rats and dogs. J Pharmacobio-dynamics 1985; 8 (12): 1006-17
28. Geromel V, Darin N, Chrétien D, et al. Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol Genet Metab 2002 Sep-Oct; 77 (1-2): 21-30
29. Seznec H, Simon D, Monassier L, et al. Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia. Human Molec Genet 2004; 13: 1017-24
30. Rustin P, von Kleist-Retzow JC, Chantrel-Groussard K, et al. Effect of idebenone on cardiomyopathy in Friedreich's ataxia: a preliminary study. Lancet 1999; 354: 477-9
31. Rustin P, Bonnet D, Rötig A, et al. Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial. Neurology 2004; 6: 524-5
32. Rustin P, Rötig A, Munnich A, et al. Heart hypertrophy and function are improved by idebenone in Friedreich's ataxia. Free Rad Res 2002; 36: 467-9
33. Schöls L, Vorgerd M, Schillings M, et al. Idebenone in patients with Friedreich ataxia. Neurosci Lett 2001; 306: 169-72
34. Filla A, Moss AJ. Idebenone for treatment of Friedreich's ataxia? Neurology 2003; 60: 1569-70
35. Buyse G, Mertens L, Di Salvo G, et al. Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring. Neurology 2003; 60: 1679-81
36. Artuch R, Aracil A, Mas A, et al. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics 2002; 33: 190-3
37. Mariotti C, Solari A, Torta D, et al. Idebenone treatment in Friedreich patients: one-year-long randomized placebocontrolled trial. Neurology 2003; 60: 1676-9
38. Hausse AO, Aggoun Y, Bonnet D, et al. Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia. Heart 2002; 87: 346-9
39. Di Prospero NA, Baker A, Jeffries N, et al. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial. Lancet Neurol 2007; 6: 878-86
40. Di Prospero NA, Sumner CJ, Penzak SR, et al. Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. Arch Neurol 2007; 64: 803-8
41. Pineda M, Arpa J, Montero R, et al. Idebenone treatment in paediatric and adult patients with Friedreich ataxia: long-term follow-up. Eur J Paediatr Neurol 2008 Nov; 12 (6): 470-5
42. Ribaï P, Pousset F, Tanguy ML, et al. Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up. Arch Neurol 2007; 64: 558-64
43. Myers L, Farmer JM, Wilson RB, et al. Antioxidant use in Friedreich ataxia. J Neurol Sci 2008; 267: 174-6
44. Lynch DR, Farmer JM, Wilson RL, et al. Performance measures in Friedreich ataxia: potential utility as clinical outcome tools. Movement Dis 2005; 20: 777-82
45. Lynch DR, Farmer JM, Tsou AY, et al. Measuring Friedreich ataxia: complementary features of examination and performance measures. Neurology 2006; 66: 1711-6
46. Fahey MC, Corben LA, Collins V, et al. The 25-foot walk velocity accurately measures real world ambulation in Friedreich ataxia. Neurology 2007; 68: 705-6
47. Tauskela JS. Mitoquinone: a mitochondria-targeted antioxidant. IDrugs 2007; 10: 399-412
48. Kelso GF, Porteous CM, Coulter CV, et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chemistry 2001; 276 (7): 4588-96
49. Kelso GF, Porteous CM, Hughes G, et al. Prevention of mitochondrial oxidative damage using targeted antioxidants. Ann N Y Acad Sci 2002; 959: 263-74
50. Dhanasekaran A, Kotamraju S, Kalivendi SV, et al. Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis. J Biol Chem 2004; 279 (36): 37575-87
51. Jauslin ML, Meier T, Smith RA, et al. Mitochondria-targeted antioxidants protect Friedreich ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J 2003; 17: 1972-4
52. James AM, Cochemé HM, Smith RA, et al. Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species: implications for the use of exogenous ubiquinones as therapies and experimental tools. J Biol Chem 2005; 280: 21295-312
53. Doughan AK, Dikalov SI. Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis. Antioxid Redox Signal 2007; 9 (11): 1825-36
54. Glickstein H, El RB, Shvartsman M, et al. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 2005; 106 (9): 3242-50
55. Porcu M, Landis N, Salis S, et al. Effects of combined deferiprone and desferrioxamine iron chelating therapy in beta-thalassemia major end-stage heart failure: a case report. Eur J Heart Fail 2007; 9: 320-2
56. Liu P, Yao YN, Wu SD, et al. The efficacy of deferiprone on tissues aluminum removal and copper, zinc, manganese level in rabbits. J Inorg Biochem 2005; 99: 1733-7
57. Boddaert N, Le Quan Sang KH, Rötig A, et al. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood 2007; 110: 401-8
58. Cohen AR, Galaello R, Piga A, et al. Safety and effectiveness of long term therapy with the oral iron chelator deferiprone. Blood 2003; 102: 1583-7
59. Koeppen AH, Michael SC, Knutson MD, et al. The dentate nucleus in Friedreich's ataxia: the role of iron-responsive proteins. Acta Neuropathol 2007; 114: 163-73
60. Sturm B, Stupphann D, Kaun C, et al. Recombinant human erythropoietin: effects on frataxin expression in vitro. Eur J Clin Invest 2005; 35: 711-7
61. Boesch S, Sturm B, Hering S, et al. Friedreich's ataxia: clinical pilot trial with recombinant human erythropoietin. Ann Neurol 2007; 62: 521-4
62. Tefferi A. Pharmaceutical erythropoietin use in patients with cancer: is it time to abandon ship or just drop anchor? Mayo Clin Proc 2007; 82: 1316-8
63. Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008; 299: 914-24
64. Sytkowski AJ. Does erythropoietin have a dark side? Epo signaling and cancer cells. Sci STKE 2007 Jul; 2007 (395): pe38
65. Pollock C, Johnson DW, Hörl WH, et al. Pure red cell aplasia induced by erythropoiesis-stimulating agents. Clin J Am Soc Nephrol 2008; 3: 193-9
66. Aapro M, Leonard RC, Barnadas A, et al. Effect of once-weekly epoetin beta on survival in patients with metastatic breast cancer receiving anthracycline- and/or taxane-based chemotherapy: results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study. J Clin Oncol 2008 Feb 1; 26 (4): 592-8
67. Thomas G, Ali S, Hoebers FJ, et al. Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer. Gynecol Oncol 2008 Feb; 108 (2): 317-25
68. Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005 Sep 1; 23 (25): 5960-72
69. Cossée M, Puccio H, Gansmuller A, et al. Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum Mol Genet 2000; 9: 1219-26
70. Campuzano V, Montermini L, Lutz Y, et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 1997; 6: 1771-80
71. Wells RD. DNA triplexes and Friedreich ataxia. FASEB J 2008 Jun; 22 (6): 1625-34
72. Herman D, Jenssen K, Burnett R, et al. Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat Chem Biol 2006; 2: 551-8
73. Grant L, Sun J, Xu H, et al. Rational selection of small molecules that increase transcription through the GAA repeats found in Friedreich's ataxia. FEBS Lett 2006; 580: 5399-405
74. Burnett R, Melander C, Puckett JW, et al. DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA-TTC repeats in Friedreich's ataxia. Proc Natl Acad Sci U S A 2006; 103: 11497-502
75. Kosutic J, Zamurovic D. High-dose beta-blocker hypertrophic cardiomyopathy therapy in a patient with Friedreich ataxia. Pediatr Cardiol 2001; 26: 727-30
76. Delatycki MB, Fahey MC, Corben L, et al. Friedreich ataxia. In: Lynch DR, Farmer JM, editors. Neurogenetics: scientific and clinical advances. New York: Taylor & Francis, 2006: 299-310