LA JOLLA, Calif.—According to the Substance Abuse and Mental Health Services Administration’s 2011 National Survey on Drug Use and Health, there are about 439,000 methamphetamine abusers in the United States. An independent study conducted by the Rand Corporation estimated the economic burden of methamphetamine use in the nation at $23.4 billion in 2005. No medications currently approved by the FDA can be used to treat methamphetamine dependence.
MediciNova Inc., a biopharmaceutical company specializing in acquiring and developing novel, small-molecule therapeutics for treating diseases with unmet medical needs, in collaboration with the National Institute on Drug Abuse (NIDA), part of the U.S. National Institutes of Health, has demonstrated the utility of MN-166 (ibudilast) in methamphetamine relapse in animals and obtained the FDA’s FastTrack designation to test it in humans.
The company presented results from a completed Phase 1b trial of MN-166 in methamphetamine dependence at a symposium titled “Neuroimmune Modulation in Addiction: Preclinical and Clinical Findings” at the 50th Winter Conference on Brain Research held from Jan. 28 to Feb. 2 in Big Sky, Mont.
But it’s not just about drug addiction, either.
The MN-166 portfolio—which includes the Phase 2-staged lead drug compound and proprietary analogs—represents novel, first-in-class, non-opioid drugs for the treatment of drug addiction, progressive multiple sclerosis, amyotrophic lateral sclerosis (ALS) and pain. MN-166 is a first-in-class, orally bioavailable, small-molecule glial attenuator that suppresses proinflammatory cytokines IL-1ß, TNF-a and IL-6, and may upregulate the anti-inflammatory cytokine IL-10. It may also be a Toll-like receptor 4 functional antagonist that may contribute to its attenuation of neuroinflammation.
Dr. Keith Heinzerling, an associate professor in the Department of Family Medicine and Medical Director of the UCLA Center for Behavioral and Addiction Medicine, and Dr. Marisa Briones, a postdoctoral research fellow, presented results for the completed Phase 1b trial that evaluated MN-166 in patients with methamphetamine dependence. They concluded that ibudilast increased levels of the biomarker brain-derived neurotrophic factor (BDNF), a growth factor which helps to support the survival of existing neurons and encourages the growth of new neurons and synapses, when compared to placebo.
Additionally, ibudilast decreased levels of the proinflammatory cytokine TNFα (tumor necrosis factor) when compared to placebo; it decreased levels of the biomarker vascular cell adhesion molecule (VCAM1), which mediates leukocyte-endothelial cell adhesion and signal transduction and may play a role in the development of neurodegenerative disorders, when compared to placebo; and it was safe and well tolerated during the methamphetamine infusions. Ibudilast is currently being investigated in a Phase 2 study to determine its ability to help methamphetamine users reduce or stop use altogether.
This ibudilast study was a randomized, double-blind, placebo-controlled within-subject Phase 1b study of MN-166 in methamphetamine-dependent, non-treatment-seeking abusers. The study duration was approximately six weeks per subject.
According to Dr. Yuichi Iwaki, president and CEO of MediciNova, “We are very pleased with ibudilast’s neuroprotective and anti-neuroinflammatory effects in methamphetamine-dependent subjects. Moreover, these results validate MN-166’s neuroprotective and anti-inflammatory properties by evaluation of biomarkers for the first time in a clinical trial. Based on these findings, along with the positive safety and tolerability results, we look forward to advancing our program to further evaluate ibudilast’s potential utility in the treatment of methamphetamine dependence.”
Additionally, an abstract about MediciNova’s ongoing clinical trial of MN-166 in ALS has been accepted for presentation at the American Academy of Neurology 69th Annual Meeting to be held April 22 to 28 in Boston. The principal investigator of the study, which began in 2014, is Dr. Benjamin Rix Brooks, director of the Carolinas Neuromuscular/ALS-MDA Center in Charlotte, N.C.
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Because the nerves lose the ability to trigger specific muscles, the muscles become weak. ALS affects voluntary movement, and patients in the later stages of the disease may become totally paralyzed. Life expectancy of an ALS patient is usually two to five years. According to the ALS Association, there are about 30,000 ALS patients in the U.S. and about 5,600 people in the U.S. diagnosed with ALS annually. Riluzole is the only pharmaceutical treatment approved for ALS, but it has limited efficacy. The MediciNova study is designed to evaluate the safety, tolerability and clinical endpoint responsiveness of MN-166 when administered as an adjunct to riluzole in subjects with ALS.