Elsevier

Neuropharmacology

Volume 110, Part B, November 2016, Pages 644-653
Neuropharmacology

Invited review
Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis

https://doi.org/10.1016/j.neuropharm.2015.08.028Get rights and content
Under a Creative Commons license
open access

Highlights

  • High-dose biotin is a promising novel treatment for progressive multiple sclerosis.

  • 300 mg biotin daily improved MS-related disability in an open-label study.

  • Biotin is essential for fatty acid synthesis and energy production.

  • High-dose biotin may promote axonal remyelination by enhancing myelin production.

  • High-dose biotin may also reduce axonal hypoxia through enhanced energy production.

Abstract

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’.

Keywords

Multiple sclerosis
Biotin
Promyelinogenic agent
Virtual hypoxia

Abbreviations

ACC
acetyl-CoA carboxylase
AMN
adrenomyeloneuropathy
BBB
blood–brain barrier
BTBGD
biotin-thiamine responsive basal ganglia disease
EDSS
Expanded Disability Status Scale
HLCS
holocarboxylase synthetase
LINGO1
leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1
MCC
3-methylcrotonyl-CoA carboxylase
MS
multiple sclerosis
OPC
oligodendrocyte precursor cell
PC
pyruvate carboxylase
PCC
propionyl-CoA carboxylase
PPMS
primary progressive multiple sclerosis
RRMS
relapsing-remitting multiple sclerosis
SPMS
secondary progressive multiple sclerosis
TCA
tricarboxylic acid
THTR2
thiamine transporter 2
TW25
time to walk 25 feet

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