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

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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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Neurological Rehabilitation, “Villa Immacolata” Clinic, Strada Sammartinese 65A, 01100, Viterbo, Italy

    Antonio Costantini & Maria Immacolata Pala

  2. Department of Economics and Management, University of Tuscia, Via del Paradiso 47, 01100, Viterbo, Italy

    Tiziana Laureti

  3. University Studies Abroad Consortium, University of Tuscia, Via Santa Maria in Gradi 4, 01100, Viterbo, Italy

    Marco Colangeli

  4. Department of Medical Sciences, University of Turin, 10126, Turin, Italy

    Simona Cavalieri, Elisa Pozzi & Alfredo Brusco

  5. Medical Genetics Unit, Città della Salute e della Scienza University Hospital, 10126, Turin, Italy

    Alfredo Brusco

  6. Unit of Neurology, ASL3 Villa Scassi Hospital, Corso O. Scassi 1, 16149, Genoa, Italy

    Sandro Salvarani & Roberto Fancellu

  7. Unit of Neurology, IRCCS San Martino University Hospital IST, Largo Rosanna Benzi 10, 16132, Genoa, Italy

    Carlo Serrati & Roberto Fancellu

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  1. Antonio Costantini
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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). https://doi.org/10.1007/s00415-016-8244-7

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