Frédéric Sedel1, Caroline Papeix2, Agnès Bellanger3, Valérie Touitou4, Christine Lebrun-Frenay5, Damien Galanaud6, Olivier Gout7, Olivier Lyon-Caen2, Ayman Tourbah8. 1. Neurology Department, AP-HP, Salpêtrière Hospital, Paris, France; Neuro-Metabolic Unit and Reference Center for Lysosomal Diseases, GRC13UPMC, Pierre & Marie Curie University-Paris 6, AP-HP, Salpêtrière Hospital, Paris, France. 2. Neurology Department, AP-HP, Salpêtrière Hospital, Paris, France. 3. Pharmacy of the Pitié-Salpêtrière Hospital, Paris, France. 4. Department of Ophthalmology, AP-HP, Salpêtrière Hospital, Paris, France. 5. Department of Neurology, Pasteur Hospital, Nice, France. 6. Department of Neuroradiology, Pierre & Marie Curie University-Paris 6, Paris, France. 7. Department of Neurology, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France. 8. Neurology Department, CHU de Reims & Faculté de Médecine de Reims, Champagne-Ardennes University, France; Laboratoire de Psychopathologie et de Neuropsychologie, EA 2027 Paris VIII University, Saint Denis, France. Electronic address: atourbah@chu-reims.fr.
Abstract
BACKGROUND: No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. OBJECTIVES: The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. STUDY DESIGN: Uncontrolled, non-blinded proof of concept study METHODS: 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. RESULTS: In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. CONCLUSIONS: These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.
BACKGROUND: No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. OBJECTIVES: The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. STUDY DESIGN: Uncontrolled, non-blinded proof of concept study METHODS: 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. RESULTS: In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. CONCLUSIONS: These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.