Efficacy and Safety of Idebenone in the Treatment of Friedreich Ataxia: A Review of Early Results and Future Prospects

• Lynch DR , FarmerJM, BalcerLJ, Wilson RB: Friedreich ataxia: effects of genetic understanding on clinical evaluation and therapy. Arch. Neurol.59(5), 743–747 (2002).
   PubMed Web of Science ®Google Scholar
• Wilson R , LynchDR, FarmerJ, BrooksDG: Increased serum transferrin receptor concentrations in Friedreich ataxia.Ann. Neurol.47(5), 659–661 (2000).
   PubMed Web of Science ®Google Scholar
• Pandolfo M : Molecular Pathogenesis of Friedreich ataxia.Arch. Neurol.56(10), 1201–1208 (1999).
   PubMedGoogle Scholar
• 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.Brain104(3), 589–620 (1981).
   PubMed Web of Science ®Google Scholar
• Epstein E , FarmerJM, TsouAet al.: Health related quality of life measures in Friedreich ataxia.J. Neurol. Sci. (2008) (In press).
   Google Scholar
• Panolfo M , MonterminiL: Molecular genetics of the hereditary ataxias.Adv. Genet.38, 31–68 (1998).
   PubMed Web of Science ®Google Scholar
• Filla A , MossAJ: Idebenone for treatment of Friedreich‘s ataxia?Neurology60(10), 1569–1570 (2003).
   PubMed Web of Science ®Google Scholar
• Meyer C , SchmidG, GorlitzSet al.: Cardiomyopathy in Friedreich‘s ataxia-assessment by cardiac MRI. Mov. Disord.22(11), 1615–1622 (2007).
   PubMed Web of Science ®Google Scholar
• Campuzano V , MonterminiL, MoltòMDet al.: Friedreich‘s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science271(5254), 1423–1427 (1996).
   PubMed Web of Science ®Google Scholar
• Schulz JB , DehmerT, SchölsLet al.: Oxidative stress in patients with Friedreich ataxia. Neurology55(11), 1719–1721 (2000).
   PubMed Web of Science ®Google Scholar
• Durr A , CosseeM, AgidYet al.: Clinical and genetic abnormalities in patients with Friedreich‘s ataxia. N. Engl. J. Med.335(16), 1169–1175 (1996).
   PubMed Web of Science ®Google Scholar
• Bidichandani SI , AshizawaT, PatelPI: Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion.Am. J. Hum. Genet.60(5), 1251–1256 (1997).
   PubMed Web of Science ®Google Scholar
• Cossée M , DürrA, SchmittMet al.: Friedreich‘s ataxia: point mutations and clinical presentation of compound heterozygotes. Ann. Neurol.45(2), 200–206 (1999).
   PubMed Web of Science ®Google Scholar
• Monrós E , MoltóMD, MartínezFet al.: Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat. Am. J. Hum. Genet.61(1), 101–110 (1997).
   PubMed Web of Science ®Google Scholar
• McCormack ML , GuttmannRP, Schumann Met al.: Frataxin point mutations in two patients with Friedreich‘s ataxia and unusual clinical features. J. Neurol. Neurosurg. Psychiatry68(5), 661–664 (2000).
   PubMed Web of Science ®Google Scholar
• Cossée M , PuccioH, GansmullerAet al.: Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum. Mol. Genet.9(8), 1219–1226 (2000).
   PubMed Web of Science ®Google Scholar
• Campuzano V , MonterminiL, LutzYet al.: Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum. Mol. Genet.6, 1771–1780 (1997).
   PubMed Web of Science ®Google Scholar
• Patel PI , IsayaG: Friedreich ataxia: from GAA triplet-repeat expansion to frataxin deficiency.Am. J. Hum. Genet.69(1), 15–24, (2001).
   PubMed Web of Science ®Google Scholar
• Adamec J , RusnakF, OwenWGet al.: Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich ataxia.Am. J. Hum. Genet.67(3), 549–562 (2000).
   PubMed Web of Science ®Google Scholar
• Cavadini P , O‘NeillHA, BenadaO, IsayaG: Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia.Hum. Mol. Genet.11(3), 217–227 (2002).
   PubMed Web of Science ®Google Scholar
• Gakh O , AdamecJ, GacyAMet al.: Physical evidence that yeast frataxin is an iron storage protein. Biochemistry41(21), 6798–6804 (2002).
   PubMed Web of Science ®Google Scholar
• Muhlenhoff U , RichhardtN, RistowMet al.: The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins. Hum. Mol. Genet.11(17), 2025–2036 (2002).
   PubMed Web of Science ®Google Scholar
• Babady NE , CarelleN, WellsRDet al.: Advancements in the pathophysiology of Friedreich ataxia and new prospects for the future. Mol. Genet. Metab.92(1–2), 23–25 (2007).
   PubMed Web of Science ®Google Scholar
• Boddaert N , Le Quan Sang KH, Rötig Aet al.: Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood110(1), 401–408 (2007).
   PubMed Web of Science ®Google Scholar
• Boesch S , SturmB, HeringSet al.: Friedreich‘s ataxia: clinical pilot trial with recombinant human erythropoietin. Ann. Neurol.62, 521–524 (2007).
   PubMed Web of Science ®Google Scholar
• Herman D , JenssenK, BurnettRet al.: Histone deacetylase inhibitors reverse gene silencing in Friedreich‘s ataxia. Nat. Chem. Biol.2, 551–558 (2006).
   PubMed Web of Science ®Google Scholar
• Ribaï P , PoussetF, TanguyMLet al.: Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up. Arch. Neurol.64(4), 558–564 (2007).
   PubMedGoogle Scholar
• Lodi R , HartPE, RajagopalanBet al.: Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich ataxia. Ann. Neurol.49(5), 590–596, (2001).
   PubMed Web of Science ®Google Scholar
• Myers L , FarmerJM, WilsonRBet al.: Antioxidant use in Friedreich ataxia. J. Neuro. Sci.267(1–2), 174–176 (2008).
   PubMed Web of Science ®Google Scholar
• Jauslin ML , VertuaniS, DuriniEet al.: Protective effects of Fe-Aox29, a novel antioxidant derived from a molecular combination of idebenone and vitamin E, in immortalized fibroblasts and fibroblasts from patients with Friedreich ataxia. Mol. Cell. Biochem.302(1–2), 79–85 (2007).
   PubMed Web of Science ®Google Scholar
• Chapela SP , BurgosHI, SalazarAI, NievasI, KriguerN, StellaCA: Biochemical study of idebenone effect on mitochondrial metabolism of yeast.Cell Biol. Int.32(1), 146–150 (2008).
   PubMed Web of Science ®Google Scholar
• Idebenone: monograph. Altern. Med. Rev.6(1), 83–86 (2001).
   PubMedGoogle Scholar
• Torii H , YoshidaK, KobayashiT, TsukamotoT, TanayamaS: Disposition of idebenone (CV-2619), a new cerebral metabolism improving agent, in rats and dogs.J. Pharmacobiodyn.8(6), 457–467 (1985).
   PubMedGoogle Scholar
• Di Prospero NA , SumnerCJ, PenzakSR, RavinaB, FischbeckKH, TaylorJP: Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia.Arch. Neurol.64(6), 803–808 (2007).
   PubMedGoogle Scholar
• Barkworth MF , DydeCJ, JohnsonKI, SchnelleK: An early Phase I to determine the tolerance, safety and pharmacokinetics of idebenone following multiple oral doses.Arzneimittelforschung35(11), 1404–1407 (1985).
   Web of Science ®Google Scholar
• Hausse AO , AggounY, BonnetDet al.: Idebenone and reduced cardiac hypertrophy in Friedreich‘s ataxia. Heart87(4), 346–349 (2002).
   PubMed Web of Science ®Google Scholar
• Rustin P , BonnetD, RötigA, MunnichA, SidiD: Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial.Neurology62(3), 524–525 (2004).
   PubMed Web of Science ®Google Scholar
• Buyse G , MertensL, Di Salvo Get al.: Idebenone treatment in Friedreich‘s ataxia: neurological, cardiac, and biochemical monitoring. Neurology60(10), 1679–1681 (2003).
   PubMed Web of Science ®Google Scholar
• Mariotti C , SolariA, TortaDet al.: Idebenone treatment in Friedreich patients: One-year-long randomized placebo-controlled trial. Neurology60(10), 1676–1679 (2003).
   PubMed Web of Science ®Google Scholar
• Artuch R , AracilA, MasAet al.: Friedreich‘s ataxia: idebenone treatment in early stage patients. Neuropediatrics33(4), 190–193 (2002).
   PubMed Web of Science ®Google Scholar
• Hart PE , LodiR, RajagopalanBet al.: Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up. Arch. Neurol.62(4), 621–626 (2005).
   PubMedGoogle Scholar
• Seznec H , SimonD, MonassierLet al.: Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia. Hum. Mol. Genet.13(10), 1017–1024 (2004).
   PubMed Web of Science ®Google Scholar
• Seznec H , WilsonRB, PuccioH: 2003 International Friedreich‘s Ataxia Research Conference, 14–16 February 2003, Bethesda, MD, USA.Neuromuscul. Disord.14(1), 70–82 (2004).
   PubMedGoogle Scholar
• Di Prospero NA , BakerA, JeffriesN, FischbeckKH: Neurological effects of high-dose idebenone in patients with Friedreich‘s ataxia: a randomised, placebo-controlled trial.Lancet Neurol.6(10), 878–886 (2007).
   PubMed Web of Science ®Google Scholar
• Santoro L , PerrettiA, LanzilloBet al.: Influence of GAA expansion size and disease duration on central nervous system impairment in Friedreich‘s ataxia: contribution to the understanding of the pathophysiology of the disease. Clin. Neurophysiol.111(6), 1023–1030 (2000).
   PubMed Web of Science ®Google Scholar
• Boni J , MaugeriA, ZingaliG, RamelliL, GherardiS: Steady-state pharmacokinetics of idebenone in healthy volunteers.Arch. Gerontol. Geriatr.15(3), 197–205 (1992).
   PubMed Web of Science ®Google Scholar

Websites

• Clinicaltrials.gov. Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich‘s Ataxia (IONIA). www.clinicaltrials.gov/ct2/show/NCT00537680?term=idebenone&rank=1
   Google Scholar
• Clinicaltrials.gov. A Study Investigating the Safety and Tolerability of Deferiprone in Patients With Friedreich‘s Ataxia. http://clinicaltrials.gov/ct2/show/NCT00530127?term=deferiprone&rank=7
   Google Scholar
• Biospace. European Medicines Evaluation Agency Acceptance of Marketing Authorization Application Filing for SNT-MC17 in Friedreich‘s Ataxia www.biospace.com/news_story.aspx?NewsEntityId=66820
   Google Scholar
• Technostart.com. Press release. Santhera starts European Phase III Study with its Lead Compound SNT-MC17 (idebenone) in Friedreich‘s Ataxia. www.technostart.com/down/r_d_6848_PR-151205.pdf
   Google Scholar