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Biotin, a therapeutic approach for multiple sclerosis

In 85% of cases, multiple sclerosis ( MS ) initially evolves through relapses that resolve completely or incompletely ( relapsing-remitting multiple sclerosis or RRMS ).
However, in about 50% of cases, patients who were initially presented with a relapsing-remitting course subsequently evolve towards a progressive form ( secondary progressive multiple sclerosis or SPMS ).
In 15% of patients, the disease strikes with an immediate progressive setting without relapses ( primary progressive multiple sclerosis or PPMS ).

It is possible to distinguish two components in the pathophysiology of multiple sclerosis: (1) an inflammatory component, responsible for the attacks, and (2) a degenerative component characterized by progression with few or less inflammation ( Noseworthy et al., 2000, Compston and Coles, 2008 ).

Among hypotheses that tend to explain the cause(s) of progressive multiple sclerosis, it has been proposed that progressive degeneration could be linked to a phenomenon of virtual hypoxia caused by a mismatch between increased energy demand by the demyelinated axon and decreased energy production because of mitochondria injury ( Luessi et al., 2012, Stys et al., 2012, Witte et al., 2013 ).

While immunosuppressive or immunomodulatory therapies reducing the inflammatory reaction are mainly effective at the relapsing-remitting phase of the disease, as they decrease the number or the duration of relapses and lesion accumulation on MRI ( magnetic resonance imaging ), they only have poor efficacy on the long-term disability and only weak or no effectiveness in the progressive ( primary or secondary ) forms of the disease ( Hauser et al., 2013 ).

With regards to permanent disability, Fampridine ( Fampyra ) is the only approved symptomatic drug that improves walking speed in a subgroup of patients ( Goodman et al., 2009 ).

Up to now, no drug has been found to have any impact on the disease׳s progressive phase ( primary or secondary ).

Biotin ( or vitamin H ) is a ubiquitous water-soluble vitamin that is naturally found in many foods ( Zempleni and Mock, 1999 ). In mammals, biotin acts as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis.

High doses of Biotin have been found to be a therapeutic option in biotin responsive basal ganglia disease ( BBGD; OMIM 607483 ), an orphan neuro-metabolic disease caused by mutations in the SLC19A3 gene coding for a thiamine transporter ( Tabarki et al., 2013 ).

Patients with BBGD display severe episodes of Leigh-like encephalopathy leading to death or permanent disability and show dramatic improvement when high doses of Biotin ( 5–10 mg/kg/day ) and Thiamine are administered ( Tabarki et al., 2013 ).

In addition, researchers found that 5 patients suffering from optic neuropathies and leukoencephalopathy did respond clinically to high doses of Biotin ( Sedel et al., 2011 ).

Subsequently, researchers discovered that one of these 5 patients suffered from secondary progressive multiple sclerosis. From this starting point, high doses of Biotin were tested in 22 additional patients with primary and secondary progressive multiple sclerosis. ( Xagena )

Sedel F et al, Mult Scler Relat Disord 2015; 4 : 159–169