For years, research efforts into effective treatments for primary progressive multiple sclerosis (PPMS) have been frustrating. While we have 14 FDA-approved disease-modifying therapies (DMTs) for relapsing MS, there currently are no therapies approved for PPMS. Fortunately, it looks like a new therapy — ocrelizumab (Ocrevus), which is very similar to rituximab (Rituxan) — should be approved in December 2016 for the treatment of relapsing forms of MS and PPMS.
Research does not end there. On September 15, 2016, the International Progressive MS Alliance awarded €12.6 million ($13.7 million in U.S. dollars as of mid-October 2016) to fund three multi-year global projects to accelerate the pace of progressive MS research. Additionally, promising results from a small randomized double-blind placebo-controlled study of high-dose biotin (also known as MD1003) in the treatment of progressive MS were published in the Multiple Sclerosis Journal in September 2016.
What is biotin?
Biotin (or vitamin H) is a water-soluble B-complex vitamin that is found naturally in many foods. It acts as an essential coenzyme involved in energy metabolism and fatty acids synthesis. Data from a small open-label pilot study and the randomized trial referenced above suggest that high doses of biotin have some impact on disease progression and permanent disability in patients with progressive MS.
The recommended adequate daily intake of biotin in adults is 30 μg, according to the Food and Nutrition Board of the Institute of Medicine. The 300 mg/day dose of biotin (MD1003) used in clinical trials is 10,000-fold higher than the amount considered adequate for normal health needs. At 300 mg/day, biotin is considered by both FDA and EMA (European Medicines Agency) regulators to be an active pharmaceutical agent and the manufacturer, MedDay Pharmaceutical (Paris, France), must first carefully investigate and demonstrate the efficacy and safety of high-dose biotin as a therapeutic option in MS before it can be made available for clinical use.
Biotin in MS research
Researchers hypothesize that high-dose biotin works in progressive MS in two ways:
- by triggering myelin synthesis in oligodendrocytes and
- by enhancing brain energy production in neurons which may in turn protect against hypoxia-driven neurodegeneration.
The efficacy and safety of MD1003 is currently being studied in three placebo-controlled trials in patients with progressive MS with either spinal cord involvement or chronic visual loss after optic neuritis, and in patients with adrenomyeloneuropathy (AMN).
In a completed open-label pilot study, over 90 percent of 23 patients treated with MD1003 for two to 36 months had some degree of clinical improvement, including reductions of disability by up to 22 percent. Patients with SPMS and PPMS suffering from optic neuropathies, homonymous hemianopia, or spinal cord involvement experienced similar positive results. It generally took at least three months to see improvement after starting treatment.
Biotin and reduced MS disability
In the double-blind study mentioned above, 154 patients with progressive MS were randomized to high-dose biotin or placebo. At baseline, approximately half of the patients were using fampridine (Ampyra, the “walking drug”), 40 percent were using DMTs, and 19 percent were in a physical therapy program.
Results of this study show that MD1003 reversed MS-related disability in 12.6 percent of patients with PPMS, compared to none of the patients on placebo. The positive effect of treatment was maintained over 24 months in 77 percent of those patients who initially responded to therapy. MD1003 also reduced the proportion of patients with confirmed EDSS progression, even in those patients who switched from placebo to MD1003 after one year.
Reduced disability was determined by sustained reduction of EDSS scores and improved speed on the 25-foot timed walk. Interestingly, reduced disability measures were achieved more frequently in patients NOT using fampridine and in those with lower baseline disability.
During the placebo-controlled phase of the trial, 12 patients on MD1003 and nine on placebo discontinued treatment due to adverse events. During the extension phase, an additional 21 patients discontinued treatment. A total of 27 percent of participants withdrew at some point due to side-effects, including mucocutaneous rash, asthenia, muscle spasms, abdominal pain, libido disorder, overdose, dry mouth, intracranial hemorrhage, mental disorder, extrasystoles, muscle spasticity, weight loss, breast cancer, and myopathy. One patient withdrew due to pregnancy and one was lost to suicide (determined to not be treatment-related).
Biotin and unexpected side-effects
Rather than having an anti-inflammatory effect on the central nervous system, it is possible that high-dose biotin may actually be pro-inflammatory. Four patients using biotin experienced relapses and there were more new or enlarging MRI lesions among patients in the MD1003 group than the placebo group. Researchers suggest that future trials should include careful assessment of MRI activity to rule out an unwanted pro-inflammatory effect of biotin on the brain.
Research has also revealed that megadoses of biotin interfere with biotin-based laboratory tests such as thyroid function tests. A patient with PPMS using biotin was misdiagnosed with Graves’ disease without any symptoms of hyperthyroidism based on laboratory results. Researchers suggest that stopping biotin supplementation for at least two days may be enough to avoid major misdiagnoses. Use of non-biotin-based laboratory assays in patients taking MD1003 may also be recommended.
Before any person with MS decides to go purchase and consume megadoses of biotin, it is very important to realize that the formulation of biotin used in clinical trials may differ significantly from the supplements you can buy at the local grocery store. It is best to discuss your options with your neurologist and always report any over-the-counter medications or supplements with your doctor.
See more helpful articles:
Redefining MS: New Phenotypes Better Describe Stages of Disease
Is Ocrelizumab The Next Game-Changer in MS Treatments?
MS Diet and Nutritional Approaches to Treatment
Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2015 Sep 5. pii: S0028-3908(15)30073-3. doi: 10.1016/j.neuropharm.2015.08.028. [Epub ahead of print] Review.
Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015 Mar;4(2):159-69. doi: 10.1016/j.msard.2015.01.005. Epub 2015 Jan 24.
Tourbah A, Lebrun-Frenay C, Edan G, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study. Mult Scler. 2016 Sep 1. pii: 1352458516667568. [Epub ahead of print]