Fresh from the Multiple Sclerosis Association of America (MSAA) is the 2014 MS Research Update, published each year, MS Research Update highlights recent research and approved therapies in the treatment of multiple sclerosis. Although the report, which was compiled mainly by Stephen Krieger, M.D., and Diana Schneider, Ph.D., details a broad range of medications, this article will focus on some of the new therapeutics under investigation, including those for relapse-remitting, primary-progressive, and secondary-progressive multiple sclerosis.
One biologic under evaluation is “anti-LINGO-1” (BIIB033), an agent that may be able to reverse demyelination of axons. Anti-LINGO-1 blocks LINGO-1, a protein in the central nervous system that prevents myelination and survival of neurons. LINGO-1 exists in the body to provide a sort of “checks and balances” to prevent malignancies, but in multiple sclerosis, this negative regulation actually prevents the body from healing itself. Initial Phase I trials using intravenous injections of anti-LINGO-1 showed that the agent was well tolerated in adults with relapsing or secondary-progressive multiple sclerosis. Two Phase II trials were launched in 2013; the first is recruiting patients with newly-diagnosed multiple sclerosis involving the visual pathways, and the second is looking to recruit 400 patients. These Phase II trials will evaluate remyelination and the extent of improvement in disability, respectively. Anti-LINGO-1 does not reduce relapses or prevent new MRI lesions, so the second trial is co-administering Avonex and using functional assessments of the effects of multiple sclerosis.
A second therapeutic studied in Germany is erythropoietin, a hormone naturally produced by the kidneys to promote erythropoiesis (red blood cell formation in the bone marrow). Animal studies showed neuroprotective effects, and a Phase I/IIa pilot study showed that high-dose erythropoietin improved cognitive performance and motor function. Researchers are still studying erythropoietin, both on its own and as an adjunct treatment for optic neuritis.
Another drug emulating the body’s own protein production is Idebenone (Catena®, Sovrima®), a drug similar to coenzyme Q10, which is produced for use in the electron transport chain as an electron sink. It also acts as an antioxidant, which is why Idebenone is postulated to reduce oxidative stress that damages nerves and the immune system. This postulation will soon be supported or demoted: a double-blind placebo-controlled Phase I/II clinical trial began in July 2009 and is scheduled to end in September 2016. It is still recruiting patients with primary-progressive multiple sclerosis and is sponsored by the National Institute of Neurological Disorders and Stroke.
A sort of “therapeutic vaccine” is also being developed to treat multiple sclerosis. MIS416 is a potent activator of the innate immune system and has been previously tested in cancer and acquired infections in an attempt to enhance the inherent capacity of the immune system to fight disease. It completed Phase I/II trials in 2012, and interim results showed MIS416 to be well-tolerated by patients with primary-progressive and secondary-progressive multiple sclerosis. Eight of ten patients with secondary-progressive multiple sclerosis showed some improvement after 12 weeks of treatment with MIS416.
Another unique development is transdermal peptides. A Polish study evaluated the safety and efficacy of three myelin peptides (MBP 85-99, PLP 139-151, and MOG) in 30 individuals with relapse-remitting multiple sclerosis. The low-dose group, which received 1 mg of each of the three peptides through a transdermal patch, had a relapse-free rate of 56%, whereas the placebo group had a relapse-free rate of only 10% after one year of treatment. Further studies may be pursued.
This list of new therapeutics is by no means comprehensive, but a number of unique treatments have been highlighted. Many of the drugs discussed are being investigated in patients with primary-progressive and/or secondary-progressive multiple sclerosis, which gives hope to these patients, as most approved drugs are indicated for relapse-remitting multiple sclerosis, only. The full report can be found on MSAA’s website.