Researchers are reporting what they call "the first clinical study to show evidence of proof of biology for remyelination in multiple sclerosis [MS] with a drug therapy."
The research team from Biogen report that patients with optic neuritis (often the first symptom of MS) who were given the monoclonal antibody BIIB033 had improved conduction of electrical impulses along the optic nerve between the retina and the brain.
Lead author Diego Cadavid, MD, Biogen Inc, Cambridge, Massachusetts, explained to Medscape Medical News that eyes normally transmit visual information to the brain in around 100 milliseconds. During an episode of optic neuritis, this may be delayed by 15 to 40 milliseconds. This delay is known as latency and is caused by loss of myelin in the optic nerve.
"Patients in this study who were given BIIB033 had an improvement of 40% in latency compared with placebo, and they were twice as likely to get back to normal times. This is giving us confidence that the drug is active and remyelination is occurring," Dr Cadavid said.
"This is the first time that evidence has been seen in humans that we might be able to repair myelin with a drug treatment. This is very exciting," he added.
Full results will be presented at next week's American Association of Neurology (AAN) 67th Annual Meeting.
Commenting on the study for Medscape Medical News, Jeffrey Cohen, MD, Cleveland Clinic Foundation, Ohio, noted that acute optic neuritis has been proposed as an experimental model system to carry out preliminary studies of potential neuroprotective or repair promoting strategies.
"In this study, the monoclonal antibody demonstrated improved conduction in the optic nerve measured by visual evoked potentials (ie, potential repair) but no improvement in optical coherence tomography parameters which measure neuronal damage in the retina," Dr Cohen said.
He added that he thought the results were "promising" and he was looking forward to hearing more details. "Also, future studies will be needed to determine whether these results can be extrapolated to chronic lesions and/or progressive MS."
Targeting the LINGO-1 Protein
Dr Cadavid explained that the monoclonal antibody used in this study is targeted to the LINGO-1 protein expressed only in the central nervous system in axons of neurons and oligodendrocyte progenitor cells (OPCs) which produce myelin.
"The theory is that in MS, myelin is not produced as these OPCs are not differentiating properly. Scientists at Biogen identified the LINGO-1 protein as having a key role inhibiting the differentiation of OPCs. The monoclonal antibody targets the LINGO-1 protein so allows the cells to differentiate better and produce myelin again," he said.
Laboratory and animal studies have shown enhancement of myelination with this agent, and a phase 1 safety study has also been completed, Dr Cadavid reported.
The current study — known as RENEW — is a phase 2 study looking at whether the drug facilitates new myelin production. "And the results suggest that it does," he added.
RENEW involved 82 patients with a first unilateral acute optic neuritis episode. "This is often the first symptom of MS so this is as early as you can ever identify anyone with MS," Dr Cadavid said.
They completed treatment with high-dose steroids and were then randomly assigned to 100 mg/kg BIIB033 intravenously or placebo once every 4 weeks (six doses total).
Remyelination was evaluated by recovery of optic nerve conduction latency using full-field visual evoked potential compared with the unaffected fellow eye at baseline.
In the intention-to-treat analysis, latency recovery improved by 3.48 milliseconds (P = .33) at 24 weeks and 6.06 milliseconds (P = .07) at 32 weeks with BIIB033.
In the per protocol analysis these values became significant, with latency recovery improving by 7.55 milliseconds at 24 weeks (P = .05) and 9.13 milliseconds (P = .01) at 32 weeks.
In addition, 53% of BIIB033 recipients got back to normal scores compared with 26% of placebo recipients. However, the drug did not affect amplitude (the strength of the information transmitted).
Neuroprotection was studied by measuring the thickness of the retinal nerve fiber layer and ganglion cell layer by using spectral-domain optical coherence tomography and the change in low-contrast letter acuity. No differences in these endpoints were seen.
Treatment-related serious adverse events were two cases of infusion-related hypersensitivity reactions and one asymptomatic transient elevation in liver aminotransferase levels.
"These results should encourage more groups to move into the space of reparative neurological therapies," Dr Cadavid suggested.
A second phase 2 study — SYNERGY — is now examining the use of BIIB033 in patients with definite MS of different severities. "This will tell us which population this drug may help the most," Dr Cadavid commented.
The study was supported by Biogen Inc. Dr Cadavid is an employee of Biogen.
American Academy of Neurology (AAN) 67th Annual Meeting, Washington, DC. Abstract 9208. To be presented on April 22, 2015.
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Cite this: 'First Clinical Evidence' of Remyelination in MS - Medscape - Apr 16, 2015.