Article related to MN-166 mechanism of action included in PNAS USA

Jul 8 2010

MediciNova Inc, a biopharmaceutical company publicly traded on the NASDAQ Global Market (Nasdaq:MNOV) and the Hercules Market of the Osaka Securities Exchange (Code Number:4875), today reported that the June 22, 2010 issue of Proceedings of the National Academy of Sciences (PNAS) USA included an article related to the mechanism of action of MN-166 (ibudilast), as an emerging therapeutic for neurological disorders. The research was lead by Dr. Elias Lolis at Yale University, and the article identifies Macrophage Migration Inhibitor Factor (MIF) as a potent and selective target for ibudilast which likely accounts for some of the drug's anti-inflammatory and neuroprotective action. MIF is one of the oldest-known pro-inflammatory cytokines thought to be involved in a number of serious medical conditions including severe systemic inflammation, autoimmunity and neuronal death and dysfunction following spinal cord injury. 

In the article, Dr. Lolis and collaborators describe the differentiated means by which ibudilast and its closely related novel analog, AV1013, inhibit MIF action. The investigators applied biological, biochemical and physical-chemical approaches demonstrating that ibudilast and AV1013 inhibit MIF's enzymatic and biologic action by interacting with the MIF protein at a region that is not considered the "active" site. Rather, they result in a change in the protein structure and subsequent inhibition of MIF activity. Accordingly, the identification that MN-166 and AV1013 selectively and potently inhibit MIF provides insights to mechanisms whereby these drug candidates may provide benefit in multiple sclerosis, neuropathic pain and drug addiction; neurological conditions that may share common disease pathways. Moreover, ibudilast has shown efficacy in animal models and early-stage human clinical trials in these conditions.

Dr. Lolis' lab at Yale University is one of the leading research groups studying MIF biochemistry and biology and his group and collaborators spent nearly three years developing the approaches and obtaining the data presented in the PNAS article. He noted that, "Our studies reveal an allosteric site explaining the mechanism of action of these drug candidates and additionally identifying a new potential site for drug discovery targeting MIF-mediated diseases."  Dr. Kirk Johnson, MediciNova's Chief Scientific Officer and a co-author of the article, added, "These research findings highlight the unique character of these drug candidates and, given the correlation of MIF inhibition and clinical drug levels, aid our understanding of MN-166 clinical action." MN-166 has completed a phase 2 proof-of-concept trial in which its potential neuroprotective utility in progressive multiple sclerosis was first illustrated and recently reported in Neurology. Additionally, MN-166 was studied in a phase 1b/2a trial in chronic neuropathic pain and is currently being evaluated in a phase 1b/2a trial for opioid withdrawal in heroin addicts. Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova noted that, "We are pleased with the research and clinical development progress with MN-166 and analogs and hope to expand clinical testing with corporate partner participation."