title: Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia.
abstract: 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.
authors.affiliation: Department of Neurological Rehabilitation, "Villa Immacolata" Clinic, Strada Sammartinese 65A, 01100, Viterbo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Costantini
authors.affiliation: Department of Economics and Management, University of Tuscia, Via del Paradiso 47, 01100, Viterbo, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Laureti
authors.affiliation: Department of Neurological Rehabilitation, "Villa Immacolata" Clinic, Strada Sammartinese 65A, 01100, Viterbo, Italy.
authors.forename: Maria Immacolata
authors.initials: MI
authors.lastname: Pala
authors.affiliation: University Studies Abroad Consortium, University of Tuscia, Via Santa Maria in Gradi 4, 01100, Viterbo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Colangeli
authors.affiliation: Department of Medical Sciences, University of Turin, 10126, Turin, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cavalieri
authors.affiliation: Department of Medical Sciences, University of Turin, 10126, Turin, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pozzi
authors.affiliation: Department of Medical Sciences, University of Turin, 10126, Turin, Italy.|Medical Genetics Unit, Città della Salute e della Scienza University Hospital, 10126, Turin, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Brusco
authors.affiliation: Unit of Neurology, ASL3 Villa Scassi Hospital, Corso O. Scassi 1, 16149, Genoa, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Salvarani
authors.affiliation: Unit of Neurology, IRCCS San Martino University Hospital IST, Largo Rosanna Benzi 10, 16132, Genoa, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Serrati
authors.affiliation: Unit of Neurology, ASL3 Villa Scassi Hospital, Corso O. Scassi 1, 16149, Genoa, Italy. roberto.fancellu@hsanmartino.it.|Unit of Neurology, IRCCS San Martino University Hospital IST, Largo Rosanna Benzi 10, 16132, Genoa, Italy. roberto.fancellu@hsanmartino.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fancellu
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004452:Echocardiography; D005260:Female; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D013831:Thiamine / Q000627:therapeutic use*; D013997:Time Factors; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D014803:Vitamin B Complex; D013831:Thiamine
keywords: Friedreich ataxia; Spinocerebellar ataxia; Thiamine; Triplet expansion diseases