Antibody Therapies in Clinical Trials: Key to Remyelination?

Myelin repair strategies are being pursued to repair old myelin damage in multiple sclerosis patients and to improve remyelination after an acute exacerbation.  Encouraging to see these potential remyelinating treatments enter clinical trial phases! Clearly, a huge need is treatment to repair myelin and hopefully improve disability for those living with MS.

Through screening over 125,000 Mayo Clinic patient blood samples, a human monoclonal antibody was found that promoted remyelination in animal models of MS.  A phase 1, multi-center, double-blind randomized study was conducted using a recombinant version of this antibody, rHIgM22.  A single dose of rHIgM22 was given in the vein to 55 MS patients and 17 patients received placebo.  Headache and contact dermatitis were reported, but no MRI or laboratory safety issues.  The MS Center for Innovations in Care at Missouri Baptist Medical Center was one of the sites for this phase 1 clinical trial.  A second phase 1 trial is planned to assess the safety and tolerability of rHIgM22 immediately following a relapse.

LINGO-1 is a glycoprotein on neurons and oligodendrocytes (myelin-making cells) in the central nervous system that blocks myelination. In the RENEW Trial, 82 patients with acute optic neuritis affecting one eye were randomized anti-LINGO-1 antibody BIIB033 or placebo infusions every 4 weeks for 6 total doses. Anti-LINGO-1 treatment had better outcomes than placebo on the full-field visual evoked potentials (P=0.05).  An ongoing phase 2 trial of anti-LINGO-1 treatment is being examined in patients with relapsing multiple sclerosis while staying on Avonex.

Semaphorin 4D signaling blocks remyelination. Anti-semaphorin 4D (Anti-SEMA 4D) monoclonal antibody protects against loss of myelin and enhancing myelin repair in animal models of MS.  A phase 1 study of VX15/2503, an anti-SEMA 4D antibody, showed that the antibody treatment was well-tolerated without serious safety issues.