Sedel Frédéric, Bernard Delphine, Mock Donald M, Tourbah Ayman
MedDay Pharmaceuticals, ICM-Brain and Spine Institute-IPEPs, Groupe Hospitalier Pitié Salpêtrière, 47 Boulevard de l'Hopital, 75013 Paris, France.
Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA.
Neuropharmacology. 2016 Nov;110(Pt B):644-653. doi: 10.1016/j.neuropharm.2015.08.028. Epub 2015 Sep 5.
Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.
进行性多发性硬化症（MS）是一种严重致残的神经系统疾病，迫切需要有效的治疗方法。最近，高剂量生物素已成为一种有前景的针对患者的治疗方法。初步临床数据表明，每日高达300毫克的生物素剂量可改善MS相关残疾的客观指标。在本文中，我们回顾了生物素的生物学特性，并探讨了这种普遍存在的辅酶的特性，这些特性可能解释了进行性MS患者中所见的令人鼓舞的反应。进行性MS患者神经功能残疾的逐渐恶化是由轴突逐渐丧失或损伤引起的。MS中轴突丧失的触发因素可能包括髓鞘的炎性脱髓鞘和神经元内虚拟缺氧状态引起的原发性神经变性。因此，针对这两种病理过程可能对进行性MS的治疗有效。生物素是参与脂肪酸合成和能量产生的五种羧化酶的必需辅助因子。我们假设高剂量生物素通过两种不同且互补的机制在进行性MS患者中发挥治疗作用：通过增强髓鞘生成促进轴突再髓鞘化，以及通过增强能量产生减少轴突缺氧。本文是名为“健康与疾病中的少突胶质细胞”特刊的一部分。
