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Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia


Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic metabolism; its deficiency causes disorders affecting both the peripheral and central nervous system. Previous studies reported low thiamine levels in cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia (FRDA). We investigated the effect of long-term treatment with thiamine in FRDA, evaluating changes in neurological symptoms, echocardiographic parameters, and plasma FXN mRNA levels. Thirty-four consecutive FRDA patients have been continuously treated with intramuscular thiamine 100 mg twice a week and have been assessed with the Scale for the Assessment and Rating of Ataxia (SARA) at baseline, after 1 month, and then every 3 months during treatment. Thiamine administration ranged from 80 to 930 days and was effective in improving total SARA scores from 26.6 ± 7.7 to 21.5 ± 6.2 (p < 0.02). Moreover, deep tendon reflexes reappeared in 57 % of patients with areflexia at baseline, and swallowing improved in 63 % of dysphagic patients. Clinical improvement was stable in all patients, who did not show worsening even after 2 years of treatment. In a subgroup of 13 patients who performed echocardiogram before and during treatment, interventricular septum thickness reduced significantly (p < 0.02). Frataxin mRNA blood levels were modestly increased in one-half of treated patients. We suppose that a focal thiamine deficiency may contribute to a selective neuronal damage in the areas involved in FRDA. Further studies are mandatory to evaluate thiamine role on FXN regulation, to exclude placebo effect, to verify our clinical results, and to confirm restorative and neuroprotective action of thiamine in FRDA.

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  1. 1.

    Pandolfo M (2012) Friedreich ataxia. Handb Clin Neurol 103:275–294

    PubMed  Article  Google Scholar 

  2. 2.

    Puccio H, Anheim M, Tranchant C (2014) Pathophysiogical and therapeutic progress in Friedreich ataxia. Rev Neurol (Paris) 170(5):355–365

    CAS  Article  Google Scholar 

  3. 3.

    Collins A (2013) Clinical neurogenetics: friedreich ataxia. Neurol Clin 31(4):1095–1120

    PubMed  Article  Google Scholar 

  4. 4.

    Corben LA, Lynch D, Pandolfo M, Schulz JB, Delatycki MB, Clinical Management Guidelines Writing Group (2014) Consensus clinical management guidelines for Friedreich ataxia. Orphanet J Rare Dis 30(9):184. doi:10.1186/s13023-014-0184-7

    Article  Google Scholar 

  5. 5.

    Ilg W, Bastian AJ, Boesch S, Burciu RG, Celnik P, Claaßen J, Feil K, Kalla R, Miyai I, Nachbauer W, Schöls L, Strupp M, Synofzik M, Teufel J, Timmann D (2014) Consensus paper: management of degenerative cerebellar disorders. Cerebellum 13(2):248–268. doi:10.1007/s12311-013-0531-6

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Sechi G, Serra A (2007) Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 6:442–455

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Mulholland PJ (2006) Susceptibility of the cerebellum to thiamine deficiency. Cerebellum 5(1):55–63

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Alekseeva N, McGee J, Kelley RE, Maghzi AH, Gonzalez-Toledo E, Minagar A (2014) Toxic-metabolic, nutritional, and medicinal-induced disorders of cerebellum. Neurol Clin 32(4):901–911

    PubMed  Article  Google Scholar 

  9. 9.

    Jhala SS, Hazell AS (2011) Modeling neurodegenerative disease pathophysiology in thiamine deficiency: consequences of impaired oxidative metabolism. Neurochem Int 58:248–260

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Mkrtchyan G, Aleshin V, Parkhomenko Y, Kaehne T, Luigi Di Salvo M, Parroni A, Contestabile R, Vovk A, Bettendorff L, Bunik V (2015) Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis. Sci Rep 27:12583

    Article  Google Scholar 

  11. 11.

    Gibson GE, Blass JP (2007) Thiamine-dependent processes and treatment strategies in neurodegeneration. Antioxid Redox Signal 9(10):1605–1619

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Pfeiffer RF (2014) Neurologic manifestations of malabsorption syndromes. Handb Clin Neurol 120:621–632

    PubMed  Article  Google Scholar 

  13. 13.

    Butterworth RF (2003) Thiamin deficiency and brain disorders. Nutr Res Rev 16:277–284

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Pedraza OL, Botez MI (1992) Thiamine status in inherited degenerative ataxias. J Neurol Neurosurg Psychiatry 55(2):136–137

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Poloni M, Mazzarello P, Laforenza U, Caramella C, Patrini C (1992) Thiamin contents of cerebrospinal fluid, plasma and erythrocytes in cerebellar ataxias. Eur Neurol 32(3):154–158

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Botez MI, Young SN (2001) Biogenic amine metabolites and thiamine in cerebrospinal fluid in heredo-degenerative ataxias. Can J Neurol Sci 28(2):134–140

    CAS  PubMed  Google Scholar 

  17. 17.

    Barbeau A, Butterworth RF, Ngo T, Breton G, Melançon S, Shapcott D, Geoffroy G, Lemieux B (1976) Pyruvate metabolism in Friedreich’s ataxia. Can J Neurol Sci 3(4):379–388

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Kark RA, Rodriguez-Budelli M, Blass JP (1978) Evidence for a primary defect of lipoamide dehydrogenase in Friedreich’s ataxia. Adv Neurol 21:163–180

    CAS  PubMed  Google Scholar 

  19. 19.

    Purkiss P, Baraitser M, Borud O, Chalmers RA (1981) Biochemical and clinical studies in Friedreich’s ataxia. J Neurol Neurosurg Psychiatry 44:574–580

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Gledhill RF, Labadarios D (1984) Biochemical vitamin deficiencies in Friedreich’s ataxia. J Neurol Neurosurg Psychiatry 47(1):111–112

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Costantini A, Giorgi R, D’Agostino S, Pala MI (2013) High dose thiamine improves the symptoms of Friedreich’s ataxia. BMJ Case Rep. doi:10.1136/bcr-2013-009424 (published online first: 22 May)

    Google Scholar 

  22. 22.

    Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski S, van de Warrenburg BP, Dürr A, Klockgether T, Fancellu R (2006) Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66(11):1717–1720

    PubMed  Article  Google Scholar 

  23. 23.

    Klockgether T, Lüdtke R, Kramer B, Abele M, Bürk K, Schöls L, Riess O, Laccone F, Boesch S, Lopes-Cendes I, Brice A, Inzelberg R, Zilber N, Dichgans J (1998) The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain 121:589–600

    PubMed  Article  Google Scholar 

  24. 24.

    Brusse E, Brusse-Keizer MG, Duivenvoorden HJ, van Swieten JC (2011) Fatigue in spinocerebellar ataxia: patient self-assessment of an early and disabling symptom. Neurology 76(11):953–959

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B (1997) International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci 145(2):205–211

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Lu J, Frank EL (2008) Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem 54(5):901–906

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Reetz K, Dogan I, Costa AS, Dafotakis M, Fedosov K, Giunti P, Parkinson MH, Sweeney MG, Mariotti C, Panzeri M, Nanetti L, Arpa J, Sanz-Gallego I, Durr A, Charles P, Boesch S, Nachbauer W, Klopstock T, Karin I, Depondt C, vom Hagen JM, Schöls L, Giordano IA, Klockgether T, Bürk K, Pandolfo M, Schulz JB (2015) Biological and clinical characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data. Lancet Neurol 14(2):174–182

    PubMed  Article  Google Scholar 

  28. 28.

    Strawser CJ, Schadt KA, Lynch DR (2014) Therapeutic approaches for the treatment of Friedreich’s ataxia. Expert Rev Neurother 14(8):949–957

    PubMed  Article  Google Scholar 

  29. 29.

    Di Prospero NA, Baker A, Jeffries N, Fischbeck KH (2007) Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: a randomised, placebo-controlled trial. Lancet Neurol 6(10):878–886

    PubMed  Article  Google Scholar 

  30. 30.

    Lynch DR, Perlman SL, Meier T (2010) A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol 67(8):941–947

    PubMed  Article  Google Scholar 

  31. 31.

    Mariotti C, Nachbauer W, Panzeri M, Poewe W, Taroni F, Boesch S (2013) Erythropoietin in Friedreich ataxia. J Neurochem 126(Suppl 1):80–87

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Boesch S, Nachbauer W, Mariotti C, Sacca F, Filla A, Klockgether T, Klopstock T, Schöls L, Jacobi H, Büchner B, vom Hagen JM, Nanetti L, Manicom K (2014) Safety and tolerability of carbamylated erythropoietin in Friedreich’s ataxia. Mov Disord 29(7):935–939

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Pandolfo M, Arpa J, Delatycki MB, Le Quan Sang KH, Mariotti C, Munnich A, Sanz-Gallego I, Tai G, Tarnopolsky MA, Taroni F, Spino M, Tricta F (2014) Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial. Ann Neurol 76(4):509–521

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Gottesfeld JM, Rusche JR, Pandolfo M (2013) Increasing frataxin gene expression with histone deacetylase inhibitors as a therapeutic approach for Friedreich’s ataxia. J Neurochem 126(Suppl 1):147–154

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Soragni E, Miao W, Iudicello M, Jacoby D, De Mercanti S, Clerico M, Longo F, Piga A, Ku S, Campau E, Du J, Penalver P, Rai M, Madara JC, Nazor K, O’Connor M, Maximov A, Loring JF, Pandolfo M, Durelli L, Gottesfeld JM, Rusche JR (2014) Epigenetic therapy for Friedreich ataxia. Ann Neurol 76(4):489–508

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Libri V, Yandim C, Athanasopoulos S, Loyse N, Natisvili T, Law PP, Chan PK, Mohammad T, Mauri M, Tam KT, Leiper J, Piper S, Ramesh A, Parkinson MH, Huson L, Giunti P, Festenstein R (2014) Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich’s ataxia: an exploratory, open-label, dose-escalation study. Lancet 384(9942):504–513

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Romano S, Coarelli G, Marcotulli C, Leonardi L, Piccolo F, Spadaro M, Frontali M, Ferraldeschi M, Vulpiani MC, Ponzelli F, Salvetti M, Orzi F, Petrucci A, Vanacore N, Casali C, Ristori G (2015) Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 14(10):985–991

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Zesiewicz TA, Sullivan KL, Gooch CL, Lynch DR (2009) Subjective improvement in proprioception in 2 patients with atypical Friedreich ataxia treated with varenicline (Chantix). J Clin Neuromuscul Dis 10(4):191–193

    PubMed  Article  Google Scholar 

  39. 39.

    Yiu EM, Tai G, Peverill RE, Lee KJ, Croft KD, Mori TA, Scheiber-Mojdehkar B, Sturm B, Praschberger M, Vogel AP, Rance G, Stephenson SE, Sarsero JP, Stockley C, Lee CY, Churchyard A, Evans-Galea MV, Ryan MM, Lockhart PJ, Corben LA, Delatycki MB (2015) An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels. J Neurol 262(5):1344–1353

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Marelli C, Figoni J, Charles P, Anheim M, Tchikviladze M, Vincitorio CM, du Montcel ST, Brice A, Golmard JL, Dürr A (2012) Annual change in Friedreich’s ataxia evaluated by the Scale for the Assessment and Rating of Ataxia (SARA) is independent of disease severity. Mov Disord 27(1):135–138

    PubMed  Article  Google Scholar 

  41. 41.

    Bürk K, Mälzig U, Wolf S, Heck S, Dimitriadis K, Schmitz-Hübsch T, Hering S, Lindig TM, Haug V, Timmann D, Degen I, Kruse B, Dörr JM, Ratzka S, Ivo A, Schöls L, Boesch S, Klockgether T, Klopstock T, Schulz JB (2009) Comparison of three clinical rating scales in Friedreich ataxia (FRDA). Mov Disord 24(12):1779–1784

    PubMed  Article  Google Scholar 

  42. 42.

    Bürk K, Schulz SR, Schulz JB (2013) Monitoring progression in Friedreich ataxia (FRDA): the use of clinical scales. J Neurochem 126(Suppl 1):118–124

    PubMed  Article  Google Scholar 

  43. 43.

    Arpa J, Sanz-Gallego I, Rodríguez-de-Rivera FJ, Domínguez-Melcón FJ, Prefasi D, Oliva-Navarro J, Moreno-Yangüela M (2014) Triple therapy with deferiprone, idebenone and riboflavin in Friedreich’s ataxia—open-label trial. Acta Neurol Scand 129(1):32–40

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Arpa J, Sanz-Gallego I, Rodríguez-de-Rivera FJ, Domínguez-Melcón FJ, Prefasi D, Oliva-Navarro J, Moreno-Yangüela M, Pascual-Pascual SI (2013) Triple therapy with darbepoetin alfa, idebenone, and riboflavin in Friedreich’s ataxia: an open-label trial. Cerebellum 12(5):713–720

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Seyer L, Greeley N, Foerster D, Strawser C, Gelbard S, Dong Y, Schadt K, Cotticelli MG, Brocht A, Farmer J, Wilson RB, Lynch DR (2015) Open-label pilot study of interferon gamma-1b in Friedreich ataxia. Acta Neurol Scand 132(1):7–15

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Velasco-Sánchez D, Aracil A, Montero R, Mas A, Jiménez L, O’Callaghan M, Tondo M, Capdevila A, Blanch J, Artuch R, Pineda M (2011) Combined therapy with idebenone and deferiprone in patients with Friedreich’s ataxia. Cerebellum 10(1):1–8

    PubMed  Article  Google Scholar 

  47. 47.

    Sanz-Gallego I, Torres-Aleman I, Arpa J (2014) IGF-1 in Friedreich’s Ataxia—proof-of-concept trial. Cerebellum Ataxias 1:10

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Strupp M, Teufel J, Habs M, Feuerecker R, Muth C, van de Warrenburg BP, Klopstock T, Feil K (2013) Effects of acetyl-DL-leucine in patients with cerebellar ataxia: a case series. J Neurol 260(10):2556–2561

    PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Takei A, Hamada S, Homma S, Hamada K, Tashiro K, Hamada T (2010) Difference in the effects of tandospirone on ataxia in various types of spinocerebellar degeneration: an open-label study. Cerebellum 9(4):567–570

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Tan S, Wang RH, Niu HX, Shi CH, Mao CY, Zhang R, Song B, Sun SL, Liu XJ, Hou HM, Liu YT, Gao Y, Fang H, Kong XD, Xu YM (2015) Nerve growth factor for the treatment of spinocerebellar ataxia type 3: an open-label study. Chin Med J (Engl) 128(3):291–294

    Article  Google Scholar 

  51. 51.

    Arpa J, Sanz-Gallego I, Medina-Báez J, Portela LV, Jardim LB, Torres-Aleman I, Saute JA (2011) Subcutaneous insulin-like growth factor-1 treatment in spinocerebellar ataxias: an open label clinical trial. Mov Disord 26(2):358–359

    PubMed  Article  Google Scholar 

  52. 52.

    Coppola G, Burnett R, Perlman S, Versano R, Gao F, Plasterer H, Rai M, Saccá F, Filla A, Lynch DR, Rusche JR, Gottesfeld JM, Pandolfo M, Geschwind DH (2011) A gene expression phenotype in lymphocytes from Friedrich Ataxia patients. Ann Neurol 70:790–804

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Smithline HA, Donnino M, Greenblatt DJ (2012) Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects. BMC Clin Pharmacol 12:4

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Shi Q, Karuppagounder SS, Xu H, Pechman D, Chen H, Gibson GE (2007) Responses of the mitochondrial alpha-Ketoglutarate dehydrogenase complex to thiamine deficiency may contribute to regional selective vulnerability. Neurochem Int 50:921–931

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Uziel G, Bottacchi E, Moschen G, Giovanardi-Rossi P, Cardace G, Di Donato S (1982) Pyruvate-dehydrogenase complex in ataxic patients: enzyme deficiency in ataxic encephalopathy plus lactic acidosis and normal activity in Friedreich ataxia. Ital J Neurol Sci 3(4):317–321

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Stumpf DA, Parks JK (1979) Friedreich ataxia. II. Normal kinetics of lipoamide dehydrogenase. Neurology 29(6):820–826

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Mastrogiacomo F, LaMarche J, Dozić S, Lindsay G, Bettendorff L, Robitaille Y, Schut L, Kish SJ (1996) Immunoreactive levels of alpha-ketoglutarate dehydrogenase subunits in Friedreich’s ataxia and spinocerebellar ataxia type 1. Neurodegeneration 5(1):27–33

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Bettendorff L, Mastrogiacomo F, LaMarche J, Dozic S, Kish SJ (1996) Brain levels of thiamine and its phosphate esters in Friedreich’s ataxia and spinocerebellar ataxia type 1. Mov Disord 11(4):437–439

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Sutak R, Xu X, Whitnall M, Kashem MA, Vyoral D, Richardson DR (2008) Proteomic analysis of hearts from frataxin knockout mice: marked rearrangement of energy metabolism, a response to cellular stress and altered expression of proteins involved in cell structure, motility and metabolism. Proteomics 8(8):1731–1741

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Shi R, Proteau A, Villarroya M, Moukadiri I, Zhang L, Trempe JF, Matte A, Armengod ME, Cygler M (2010) Structural basis for Fe-S cluster assembly and tRNA thiolation mediated by IscS protein-protein interactions. PLoS Biol 8(4):e1000354. doi:10.1371/journal.pbio.1000354

    PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    Alfadhel M, Almuntashri M, Jadah RH, Bashiri FA, Al Rifai MT, Al Shalaan H, Al Balwi M, Al Rumayan A, Eyaid W, Al-Twaijri W (2013) Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases. Orphanet J Rare Dis 8:83. doi:10.1186/1750-1172-8-83

    PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Kono S, Miyajima H, Yoshida K, Togawa A, Shirakawa K, Suzuki H (2009) Mutations in a thiamine-transporter gene and Wernicke’s-like encephalopathy. N Engl J Med 360:1792–1794

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Lonsdale D (2006) A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives. Evid Based Complement Altern Med 3(1):49–59

    Article  Google Scholar 

  64. 64.

    Sedel F, Challe G, Mayer JM, Boutron A, Fontaine B, Saudubray JM, Brivet M (2008) Thiamine responsive pyruvate dehydrogenase deficiency in an adult with peripheral neuropathy and optic neuropathy. J Neurol Neurosurg Psychiatry 79(7):846–847

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Brown G (2014) Defects of thiamine transport and metabolism. J Inherit Metab Dis 37(4):577–585. doi:10.1007/s10545-014-9712-9

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Botez MI, Botez-Marquard T, Mayer P, Marchand L, Lalonde R, Reader TA (1998) The treatment of spinocerebellar ataxias: facts and hypotheses. Med Hypotheses 51:381–384

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Reddy PH, Reddy TP (2011) Mitochondria as a therapeutic target for aging and neurodegenerative diseases. Curr Alzheimer Res 8:393–409

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Meador K, Loring D, Nichols M, Zamrini E, Rivner M, Posas H, Thompson E, Moore E (1993) Preliminary findings of high-dose thiamine in dementia of Alzheimer’s type. J Geriatr Psychiatry Neurol 6:222–229

    CAS  PubMed  Article  Google Scholar 

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The authors thank the patients and their families; the staff of Units of Neurology at Villa Scassi Hospital, at San Martino University Hospital, and at Villa Immacolata Rehabilitation Center, particularly the personnel of the Women Rehabilitation Division; Dr. Davide Faga (Neurologist), Dr. Paolo Tanganelli (Neurologist, Current Director of Unit of Neurology, ASL3 Villa Scassi Hospital, Genoa), Dr. Agostino Nappo (Neurologist), Dr. Michele Mussap (Director of Lab Analysis, IRCCS San Martino University Hospital IST, Genoa), Dr. Enzo Grossi (Medical Director of Dipartimento Farma Italia Bracco S.p.a, Milan), Dr. Innocenza Berni (MD), Dr. Laura Compagnoni (MD), Dr. Mauro Brogi (MD), Dr. Pina Paolella (MD); Father Emilio Blasi, Father Emmanuel Nabaloum; Maria Pia De Santis, Umberto Morgia; Prof. Aldo Laterza (Professor of Neurology of the first author of the present paper) for support and encouragement.

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Costantini, A., Laureti, T., Pala, M.I. et al. Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia. J Neurol 263, 2170–2178 (2016).

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  • Thiamine
  • Spinocerebellar ataxia
  • Triplet expansion diseases
  • Friedreich ataxia