As researchers continue to develop a clearer understanding of the underlying causes of multiple sclerosis (MS), it is becoming increasingly apparent that the future of treating the disease is likely to center on neural protection and a reversal of the demyelination process that strips away the critical insulation surrounding denuded axons. To this end, there is currently a series of studies underway for a potential, new treatment option for MS that would directly address the need for protecting neurons so that remyelination may commence, thus leading to a slowing of the disease progression and improvement of symptoms.
Recent phase I clinical trials of a novel, experimental MS therapy based on the facilitating the remyelination process has thus far revealed positive safety and tolerance findings, which are now available in Neurology Neuroimmunology & Neuroinflammation‘s August 27, 2014 issue. This new journal published by the American Academy of Neurology is free to access and is exclusively available online.
According to previously completed studies involving animal models, this new multiple sclerosis drug called anti-LINGO-1, or BIIB033, has the potential to reverse nerve demyelination. LINGO-1 is described as a “human anti-Nogo receptor interacting protein-1 monoclonal antibody,” according to the study, and this subsequent series of phase I trials using LINGO-1 was the first to test the new formulation on human subjects. Because anti-LINGO-1 is designed to block a protein in the central nervous system that hinders myelination, this medication may accomplish what currently available MS treatments have yet to offer, which is to actually repair neurological damage.
According to the researchers, LINGO-1 is considered an emerging therapy for myelin regeneration due to the fact that it ultimately has shows to lead to “in vivo remyelination through induction of OPC differentiation and neuroprotection” in experimental immune as well as non-immune models of demyelination. Combined with a human monoclonal version of an anti-LINGO-1 antibody, which has already been developed by researchers and currently is being tested in a phase-II clinical trial as a therapy for the disease, this development, together with an increased understanding of the role that LINGO-1 plays in the myelination process, is considered by the researchers to be the impetus for a potential breakthrough, pending the outcome of current and future trials.
The published phase I clinical trial results involved 72 participants without MS, and 47 patients diagnosed with either relapsing-remitting MS, or secondary progressive MS. The researchers administered either the anti-LINGO-1 or a placebo via IV to the two groups, with the healthy group receiving one dose, and the MS group receiving two doses, two weeks apart. All of the participants from both groups were administered different concentrations of the medication, varying from 0.1 mg/kg to 100 mg/kg.
As to observable side effects of the medication, there was no significant difference between those who were on the medication and those who were on the placebo. Any observed side effects were minor and not necessarily associated with the primary indication of the drug, such as headaches, and infections of the upper respiratory and urinary tracts. There were no incidences of adverse effects or deaths, nor were there notable alterations in participants’ vital signs, EKG readings, or other safety parameters.
Those who received at least 10mg/kg of the drug retained blood concentrations comparable to those previously observed in rats that showed 90% remyelination from the drug.
The study’s author, Dr. Diego Cadavid of Cambridge, Massachusetts’ Biogen Idec, is pleased with the phase I results and has already begun work on phase II, to test if anti-LINGO-1 can restore myelination along with physical and cognitive function.
In other reports on emerging MS treatments, earlier this year, Dr. Rhonda Voskuhl of UCLA presented her findings to the American Academy of Neurology Annual Meeting on the enhanced efficacy of Copaxone combined with estriol for RRMS.