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MS research update – High-dose biotin (MD1003) investigated as a potential treatment for progressive MS – 6 December 2016

Summary

Results from a small pilot study suggested that high-dose biotin 300mg/day (MD1003) might be an effective treatment for secondary and primary progressive MS. To test this further, French researchers carried out a clinical trial to see if treatment with high-dose biotin could reduce disability.

154 people with progressive multiple sclerosis with an initial EDSS of 4.5 - 7, took capsules containing either placebo or high-dose biotin three times a day for 12 months. 13 out of 103 people (12.6%) taking high-dose biotin had reduced disability at month 9 which was maintained at month 12, compared to none of the 51 people taking placebo.

After the first 12 months, all participants took high-dose biotin for a further 12 months. At the end of the second 12 months, 19 of 133 people had reduced disability, which included 10 of the 13 people who had responded in the first year and others who had initially been taking placebo.

The study also looked at how many people had increased disability. At the end of the first 12 months, 4 out of 103 people (4.2%) taking high-dose biotin had increased EDSS, compared to 6 of 51 (13.6%) people taking placebo. At the end of the second 12 months, EDSS had increased in 9.9% of those in the biotin>biotin group compared to 31.7% in the placebo>biotin group.

The researchers conclude that high-dose biotin causes a reversal of MS-related disability in a subset of people with progressive MS.


Background

MD1003 is a highly concentrated formulation of biotin under investigation as a treatment for secondary and primary progressive multiple sclerosis (MS). It is thought that very high doses of biotin may be effective in MS by promoting myelin repair through activation of an enzyme involved in myelin synthesis and by enhancing energy production in demyelinated nerves.

A small pilot study of 23 people with primary and secondary progressive MS provided initial evidence of effectiveness and safety of high doses of biotin. This was an open study - in other words both the people with MS and their doctors knew what treatment they were receiving; this can bias the results.

To investigate high-dose biotin further, researchers carried out a clinical trial to see if treatment with high-dose biotin could reverse, that is improve, levels of disability. This is a more ambitious target than previous studies in progressive MS where the main aim of a study is to prevent further disability.

Topline results from this clinical trial were presented at a scientific meeting in 2015. Full details of the study have now been published and are summarised in this Research Update.

How this study was carried out

154 people with secondary and primary progressive MS with EDSS of 4.5 - 7 and evidence of disease worsening in the previous 2 years were recruited at study centres in France. Participants took either high-dose biotin (300mg each day) or placebo capsules three times a day for the first 12 months, then all participants took high-dose biotin for a further 12 months. Throughout both parts of the study, neither participants nor investigators knew which treatment they had taken during the first 12 months.

Participants continued with any medications or other treatments they were already taking. Approximately half of the people in each group were taking fampridine, and approximately 40% in each group were taking a disease modifying drug.

Participants visited their study centres every three months for assessments. The main measure of the study was an improvement in disability after 9 months which was still evident 3 months later at the 12 month assessment. Improvement in disability was defined as either a reduction in EDSS of 0.5 to 1 point (depending on starting level) or a 20% reduction in the time to walk 25 feet.

What was found

At the end of the first 12 months, 13 out of 103 people (12.6%) taking high-dose biotin had reduced disability, compared to none of the 51 people taking placebo. Of those whose disability improved, just 2 had an improvement in both EDSS and walking time; 8 had an improvement in EDSS only, and 3 had an improvement in walking time only.

At the end of the second 12 months, 19 out of the 133 people who had continued in the study had reduced disability, which included 10 of the 13 people who had responded in the first year and a further 9 who had initially been taking placebo.

A secondary measure was the number of people with worsening disability (increase in EDSS). The proportion of participants with increased EDSS at month 9 (and maintained at month 12) was 13.6% in the placebo group and 4.2% in the high-dose biotin group. At month 18 (maintained at month 24) the proportion increased to 31.7% in the placebo>biotin group and 9.9% in the biotin>biotin group.

There were no serious side effects although five participants taking high-dose biotin had “apparent hyperthyroidism” which had been caused by high levels of biotin in samples interfering with thyroid hormone blood tests. Mild to moderate side effects included urinary tract infections and headache and were reported for both placebo and biotin groups, suggesting that side effects were not caused by biotin.

What does it mean?

The results suggest that high-dose biotin may cause a reversal of MS-related disability in a subset of people with progressive MS. However, the numbers of people involved in the study are relatively low, making it difficult to draw firm conclusions. The data are complex and will require more detailed analysis to draw further conclusions or identify those most likely to benefit.

One question raised by an accompanying editorial is whether the improvements seen are the result of permanent improvement in MS due to remyelinaton or are temporary improvements in MS symptoms. The fact that improvements in disability tended to be apparent after 3 months would suggest an effect on symptoms rather than on the underlying MS. The researchers note that improvement in disability occurred more frequently in the high-dose biotin group for people who were not taking fampridine (Fampyra, a drug which can improve walking speed). They also note that improvement in disability was seen most often in people with a lower starting EDSS of 4.5 - 5.5 rather than 6 - 7.

Tourbah A, et al.
MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: a randomised, double-blind, placebo-controlled study.
Multiple Sclerosis Journal 2016; 22: 1719-1731.
Abstract
Read the full text of this paper

More about biotin and MD1003

Biotin, also known as vitamin B7, is a vitamin that is found in small amounts in numerous foods, including brewer's yeast, cooked eggs, sardines and nuts. Biotin is necessary for formation of fatty acids and glucose, which are used as fuels by the body. It is also important for the metabolism of amino acids and carbohydrates. A lack of biotin is rare.

It is thought that very high doses of biotin may be effective in MS by promoting myelin repair through activation of an enzyme involved in myelin synthesis and by enhancing energy production in demyelinated nerves.

High-dose biotin (MD1003) Is a highly-concentrated formulation of biotin. The doses being used in clinical trials correspond to 10,000 times the recommended daily intake of biotin. At this dose, it is not considered a food supplement and is being developed as a pharmaceutical preparation. Neurologists are warning that people should not start taking large quantities of biotin supplements which are manufactured to a lower quality than the pharmaceutical grade biotin used for this study.

Data from high-dose biotin laboratory and clinical studies were submitted to the European Medicines Agency who will assess it for effectiveness, safety and manufacturing quality standards. If the EMA are satisfied they will grant a marketing authorisation or licence. Once this has happened, MD1003 will be appraised for cost effectiveness as an NHS treatment. If all of these steps are successful, high-dose biotin could be available as an NHS treatment by late 2017, early 2018.

A further clinical trial of high-dose biotin is currently being set up which aims to recruit 300 people from North America and Europe, including study centres in Edinburgh, London and Manchester. If you are interested in taking part in this study, you should first of all speak to your MS nurse and neurologist.

More about drugs in development for progressive MS

Information about high-dose biotin, ocrelizumab, siponimod and other drugs being investigated as treatments for progressive MS can be found through our Drugs in development webpage.

Research by topic areas...

Carers

Donzé C, Lenne B, Jean Deleglise AS, et al.
EVASEP: a noninterventional study describing the perception of neurologists, patients, and caregivers on caregivers' role in the support of patients suffering from multiple sclerosis treated with subcutaneous interferon beta 1a.
Mult Scler Int. 2016;2016:4986073.
abstract
Read the full text of this paper

CCSVI

Martin N, Traboulsee AL, Machan L, et al.
Prevalence of extracranial venous narrowing on magnetic resonance venography is similar in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study.
Can Assoc Radiol J. 2016 Nov 22. pii: S0846-5371(16)30083-3. [Epub ahead of print]
abstract

Co-existing conditions

Kosmidou M, Katsanos AH, Katsanos KH, et al.
Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta-analysis.
J Neurol. 2016 Nov 22. [Epub ahead of print]
abstract

Diagnosis

Brownlee WJ, Hardy TA, Fazekas F, et al.
Diagnosis of multiple sclerosis: progress and challenges.
Lancet. 2016 Nov 23. pii: S0140-6736(16)30959-X. [Epub ahead of print]
abstract

Spelman T, Meyniel C, Rojas JI, et al.
Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice.
Mult Scler. 2016 Nov 24. pii: 1352458516679893. [Epub ahead of print]
abstract

Disease modifying drugs

Malucchi S, Capobianco M, Lo Re M, et al.
High-risk PML patients switching from natalizumab to alemtuzumab: an observational study.
Neurol Ther. 2016 Dec 3. [Epub ahead of print]
abstract
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Moreau T, Bungener C, Heinzlef O, et al.
Anxiety and coping strategy changes in multiple sclerosis patients initiating fingolimod: the GRACE prospective study.
Eur Neurol. 2016 Dec 2;77(1-2):47-55. [Epub ahead of print]
abstract

Soelberg Sorensen P.
Safety concerns and risk management of multiple sclerosis therapies.
Acta Neurol Scand. 2016 Nov 27. [Epub ahead of print]
abstract

Comi G, Radaelli M, Soelberg Sørensen P.
Evolving concepts in the treatment of relapsing multiple sclerosis.
Lancet. 2016 Nov 23. pii: S0140-6736(16)32388-1. [Epub ahead of print]
abstract

Mandal P, Gupta A, Fusi-Rubiano W, et al.
Fingolimod: therapeutic mechanisms and ocular adverse effects.
Eye (Lond). 2016 Nov 25. [Epub ahead of print]
abstract

Arroyo González R, Kita M, Crayton H, et al.
Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis.
Mult Scler. 2016 Nov 24. pii: 1352458516677589. [Epub ahead of print]
abstract

Berger T, Elovaara I, Fredrikson S, et al.
Alemtuzumab use in clinical practice: recommendations from European multiple sclerosis experts.
CNS Drugs. 2016 Nov 23. [Epub ahead of print]
abstract
Read the full text of this paper

La Mantia L, Di Pietrantonj C, Rovaris M, et al.
Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis.
Cochrane Database Syst Rev. 2016 Nov 24;11:CD009333. Review.
abstract
Read the full text of this paper

Hua LH, Cohen JA.
Considerations in the development of generic disease therapies for multiple sclerosis.
Neurol Clin Pract. 2016 Aug;6(4):369-376. Review.
abstract

Sater RA, Gudesblatt M, Kresa-Reahl K, et al.
NAPS-MS: natalizumab effects on parameters of sleep in patients with multiple sclerosis.
Int J MS Care. 2016 Jul-Aug;18(4):177-82.
abstract
Read the full text of this paper

Wingerchuk DM, Weinshenker BG.
Disease modifying therapies for relapsing multiple sclerosis.
BMJ. 2016 Aug 22;354:i3518.
abstract

Kaunzner UW, Kumar G, Askin G, et al.
A study of patients with aggressive multiple sclerosis at disease onset.
Neuropsychiatr Dis Treat. 2016 Aug 1;12:1907-12.
abstract
Read the full text of this paper

Fernández O, Arroyo R, Martínez-Yélamos S, et al.
Long-term adherence to IFN beta-1a treatment when using RebiSmart® device in patients with relapsing-remitting multiple sclerosis.
PLoS One. 2016 Aug 15;11(8):e0160313.
abstract
Read the full text of this paper

Khan O, Rieckmann P, Boyko A, et al.
Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing-remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study.
Mult Scler. 2016 Aug 8. pii: 1352458516664033. [Epub ahead of print]
abstract

Xu M, Lu X, Fang J, et al.
The efficacy and safety of teriflunomide based therapy in patients with relapsing multiple sclerosis: A meta-analysis of randomized controlled trials.
J Clin Neurosci. 2016 Nov;33:28-31.
abstract

Winkelmann A, Loebermann M, Reisinger EC, et al.
Disease-modifying therapies and infectious risks in multiple sclerosis.
Nat Rev Neurol. 2016 Apr;12(4):217-33.
abstract

Cohen JA, Khatri B, Barkhof F, et al.
Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study.
J Neurol Neurosurg Psychiatry. 2016 May;87(5):468-75.
abstract
Read the full text of this paper

Drugs in development

Schwartzbach CJ, Grove RA, Brown R, et al.
Lesion remyelinating activity of GSK239512 versus placebo in patients with relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II study.
J Neurol. 2016 Nov 25. [Epub ahead of print]
abstract
Read the full text of this paper

Menge T, Dubey D, Warnke C, et al.
Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis.
Expert Rev Neurother. 2016 Oct;16(10):1131-9.
abstract

Kappos L, Arnold DL, Bar-Or A, et al.
Safety and efficacy of amiselimod in relapsing multiple sclerosis (MOMENTUM): a randomised, double-blind, placebo-controlled phase 2 trial.
Lancet Neurol. 2016 Oct;15(11):1148-59.
abstract

Goodman AD, Gyang T, Smith AD 3rd.
Ibudilast for the treatment of multiple sclerosis.
Expert Opin Investig Drugs. 2016 Oct;25(10):1231-7.
abstract

Khoury SJ, Rochon J, Ding L, et al.
ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis.
Mult Scler. 2016 Aug 1. pii: 1352458516662727. [Epub ahead of print]
abstract

Schreiber K, Magyari M, Sellebjerg F, et al.
High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial.
Mult Scler. 2016 Aug 1. pii: 1352458516661048. [Epub ahead of print]
abstract

Epidemiology

Ventura RE, Antezana AO, Bacon T, et al.
Hispanic Americans and African Americans with multiple sclerosis have more severe disease course than Caucasian Americans.
Mult Scler. 2016 Nov 29. pii: 1352458516679894. [Epub ahead of print]
abstract
Read the full text of this paper

Families

Moberg JY, Magyari M, Koch-Henriksen N, et al.
Educational achievements of children of parents with multiple sclerosis: A nationwide register-based cohort study.
J Neurol. 2016 Nov;263(11):2229-2237.
abstract

Hinton D, Kirk S.
Living with uncertainty and hope: A qualitative study exploring parents' experiences of living with childhood multiple sclerosis.
Chronic Illn. 2016 Aug 17. pii: 1742395316664959. [Epub ahead of print]
abstract

Other treatments

Jelinek GA, De Livera AM, Marck CH, et al.
Associations of lifestyle, medication, and socio-demographic factors with disability in people with multiple sclerosis: an international cross-sectional study.
PLoS One. 2016 Aug 25;11(8):e0161701.
abstract
Read the full text of this paper

Hasanpour-Dehkordi A, Jivad N, Solati K.
Effects of yoga on physiological indices, anxiety and social functioning in multiple sclerosis patients: a randomized trial.
J Clin Diagn Res. 2016 Jun;10(6):VC01-VC05.
abstract
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Rogers KA, MacDonald M.
Therapeutic yoga: symptom management for multiple sclerosis.
J Altern Complement Med. 2015 Nov;21(11):655-9.
abstract
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Voldsgaard A, Bager P, Garde E, et al.
Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect.
Mult Scler. 2015 Nov;21(13):1723-9.
abstract

Paediatric MS

D'Amico E, Zanghì A, Patti F.
Can new chemical therapies improve the management of multiple sclerosis in children?
Expert Opin Pharmacother. 2016 Nov 30. [Epub ahead of print]
abstract

Ghezzi A, Amato MP, Makhani N, et al.
Pediatric multiple sclerosis: conventional first-line treatment and general management.
Neurology. 2016 Aug 30;87(9 Suppl 2):S97-S102.
abstract
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Amato MP, Krupp LB, Charvet LE, et al.
Pediatric multiple sclerosis: cognition and mood.
Neurology. 2016 Aug 30;87(9 Suppl 2):S82-7.
abstract
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Waldman A, Ness J, Pohl D, et al.
Pediatric multiple sclerosis: clinical features and outcome.
Neurology. 2016 Aug 30;87(9 Suppl 2):S74-81.
abstract
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Hintzen RQ, Dale RC, Neuteboom RF, et al.
Pediatric acquired CNS demyelinating syndromes: features associated with multiple sclerosis.
Neurology. 2016 Aug 30;87(9 Suppl 2):S67-73.
abstract
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Krupp LB, Rintell D, Charvet LE, et al.
Pediatric multiple sclerosis: perspectives from adolescents and their families.
Neurology. 2016 Aug 30;87(9 Suppl 2):S4-7.
abstract
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Chitnis T, Ghezzi A, Bajer-Kornek B, et al.
Pediatric multiple sclerosis: escalation and emerging treatments.
Neurology. 2016 Aug 30;87(9 Suppl 2):S103-9.
abstract
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Lanzillo R, Chiodi A, Carotenuto A, et al.
Quality of life and cognitive functions in early onset multiple sclerosis.
Eur J Paediatr Neurol. 2016 Jan;20(1):158-63.
abstract
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Prognosis

Gajofatto A, Turatti M, Bianchi MR, et al.
Benign multiple sclerosis: physical and cognitive impairment follow distinct evolutions.
Acta Neurol Scand. 2016 Mar;133(3):183-91.
abstract

Psychological aspects

Randolph JJ, Randolph JS, Wishart HA.
Association between cognitive complaints and vulnerability to environmental distraction in multiple sclerosis.
Arch Clin Neuropsychol. 2016 Dec 1. [Epub ahead of print]
abstract

Sepúlveda M, Fernández-Diez B, Martínez-Lapiscina EH, et al.
Impairment of decision-making in multiple sclerosis: A neuroeconomic approach.
Mult Scler. 2016 Nov 30. pii: 1352458516682103. [Epub ahead of print]
abstract

Lewis VM, Williams K, KoKo C, et al.
Disability, depression and suicide ideation in people with multiple sclerosis.
J Affect Disord. 2016 Oct 2. pii: S0165-0327(16)30823-0. [Epub ahead of print]
abstract

Quality of life

Jelinek GA, De Livera AM, Marck CH, et al.
Lifestyle, medication and socio-demographic determinants of mental and physical health-related quality of life in people with multiple sclerosis.
BMC Neurol. 2016 Nov 22;16(1):235.
abstract
Read the full text of this paper

Rehabilitation

Pompa A, Morone G, Iosa M, et al.
Does robot-assisted gait training improve ambulation in highly disabled multiple sclerosis people? A pilot randomized control trial.
Mult Scler. 2016 Aug 2. pii: 1352458516663033. [Epub ahead of print]
abstract

Review

Owens B.
Multiple sclerosis.
Nature. 2016 Nov 30;540(7631):S1.
abstract
Read the full text of this paper

Ontaneda D, Thompson AJ, Fox RJ, et al.
Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.
Lancet. 2016 Nov 23. pii: S0140-6736(16)31320-4. [Epub ahead of print]
abstract

Symptoms and symptom management

Jenkins TM, Toosy AT.
Optic neuritis: the eye as a window to the brain.
Curr Opin Neurol. 2016 Nov 30. [Epub ahead of print]
abstract

Veauthier C, Hasselmann H, Gold SM, et al.
The Berlin Treatment Algorithm: recommendations for tailored innovative therapeutic strategies for multiple sclerosis-related fatigue.
EPMA J. 2016 Nov 24;7:25. Review.
abstract
Read the full text of this paper

Roy S, Frndak S, Drake AS, et al.
Differential effects of aging on motor and cognitive functioning in multiple sclerosis.
Mult Scler. 2016 Nov 24. pii: 1352458516679036. [Epub ahead of print]
abstract

Pickering H, Murray J, Lin CS, et al.
Fampridine treatment and walking distance in multiple sclerosis: A randomised controlled trial.
Clin Neurophysiol. 2016 Nov 2;128(1):93-99. [Epub ahead of print]
abstract

Cortese M, Riise T, Bjørnevik K, et al.
Preclinical disease activity in multiple sclerosis: a prospective study of cognitive performance prior to first symptom.
Ann Neurol. 2016 Oct;80(4):616-24.
abstract

Brown TR, Simnad VI.
A randomized crossover trial of dalfampridine extended release for effect on ambulatory activity in people with multiple sclerosis.
Int J MS Care. 2016 Jul-Aug;18(4):170-6.
abstract
Read the full text of this paper

Newland P, Flick L, Xian H, et al.
Symptom co-occurrences associated with smoking in individuals with relapsing-remitting multiple sclerosis.
Int J MS Care. 2016 Jul-Aug;18(4):163-8.
abstract
Read the full text of this paper

Cincotta MC, Engelhard MM, Stankey M, et al.
Fatigue and fluid hydration status in multiple sclerosis: A hypothesis.
Mult Scler. 2016 Oct;22(11):1438-1443.
abstract

Stellmann JP, Jlussi M, Neuhaus A, et al.
Fampridine and real-life walking in multiple sclerosis: Low predictive value of clinical test for habitual short-term changes.
J Neurol Sci. 2016 Sep 15;368:318-25.
abstract

Campbell J, Rashid W, Cercignani M, et al.
Cognitive impairment among patients with multiple sclerosis: associations with employment and quality of life.
Postgrad Med J. 2016 Aug 10. pii: postgradmedj-2016-134071. [Epub ahead of print]
abstract

Lanza G, Ferri R, Bella R, et al.
The impact of drugs for multiple sclerosis on sleep.
Mult Scler. 2016 Aug 8. pii: 1352458516664034. [Epub ahead of print] Review.
abstract

Alali D, Ballard K, Bogaardt H.
Treatment effects for dysphagia in adults with multiple sclerosis: a systematic review.
Dysphagia. 2016 Oct;31(5):610-8.
abstract

Magnin E, Sagawa Y Jr, Chamard L, et al.
Verbal fluencies and fampridine treatment in multiple sclerosis.
Eur Neurol. 2015;74(5-6):243-50.
abstract

Vitamin D

Nielsen NM, Munger KL, Koch-Henriksen N, et al.
Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study.
Neurology. 2016 Nov 30. pii: 10.1212/WNL.0000000000003454. [Epub ahead of print]
abstract