September 10, 2014

Emerging myelin-repair drug passes phase 1 safety tests


As it stands, multiple sclerosis (MS) drug therapies have traditionally focused on reducing damage to myelin and axons. This takes the shape of therapeutics directed at modifying the disease course. Often they work by interfering with the inflammatory component of MS, resulting in less relapses and improvement in symptoms. While such approaches have proven positive for controlling the disease, researchers suggest that future work should focus on repairing the damage inflicted upon the nerve tissue. A new study published in August by Dr. Jonathan Tran and colleagues marks a potential turning point and paradigm shift for MS treatments.

This study is the first of its kind insofar as it is testing a drug called BIIB033 which targets the reparation and restoration of myelin (a process known as remyelination). BIIB033 functions by inhibiting the actions of LINGO-1, a protein which blocks myelin production. By stopping LINGO-1, BIIB033 decreases the extent to which LINGO-1 can block the repair of damaged axons and myelin in MS. 

The primary objective of the trial was to test the safety and tolerability (ability for the body to process the drug) of BIIB033 in healthy people and people living with MS.

The Study

The study involved two phase I clinical trials conducted in 72 healthy volunteers, and 47 individuals with relapse-remitting MS (RRMS) or secondary progressive MS (SPMS). The trials took place in the U.S. and Netherlands.

The first trial was a single ascending dose (SAD) study, in which the group of healthy volunteers were randomly assigned to receive single injections of either BIIB033, or a mock drug (placebo). Neither the person administering the drug nor the volunteer knew which drug they were taking, a process referred to as blinding which helps to avoid bias. The second trial was a multiple ascending dose (MAD) study, in which the MS group was randomly assigned to receive multiple injections of BIIB033 or a mock drug.

In both trials, participants were grouped and each group received increasing doses up to 100mg/kg. This enables the researchers to analyze the safety and tolerability of the drug at each dose, as demonstrated by the results of physical and neurological examinations, blood work and imaging scans conducted at each stage.


Results of the phase I clinical trials demonstrated the safety and tolerability of BIIB033 at doses up to 100 mg/kg to the extent that phase II of clinical trials can proceed. There were no serious adverse effects or deaths reported during the study. The frequency of moderate side effects, i.e., headaches, upper respiratory infections, and urinary tract infections, were similar between the group who received BIIB033 and those who received the placebo drug. Moreover, the occurrence of BIIB033 causing the body to create anti-drug antibodies, an immune response that would render the drug ineffective, was also low.


The results of the first in-human trial for a potential repair drug for MS are a true cause for optimism. However, it is necessary to consider some of the limitations faced by studies investigating remyelination therapies as they continue to move forward. For example, a tried and tested method to reliably detect and measure remyelination, especially in its early stages, remains elusive. However, the discussion as to how to concurrently explore remyelinating therapies and the technologies to measure the results of such studies is not being neglected by the scientific community and there is much to look forward to in the near future. The MS Society supports all avenues of research that will advance the search for a cure for MS, and will continue to provide updates on this work and future clinical trials involving BIIB033.


Tran, JQ et al. Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033. Neurology: Neuroimmunology and Neuroinflammation 2014 August 27 [Epub ahead of print].