On April 20, 2022 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported data demonstrating that MN-166 (ibudilast) prevents metastasis in a uveal melanoma (UM) animal model was published in the journal Molecular Cancer Research (Press release, MediciNova, APR 20, 2022, View Source [SID1234612858]).
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The publication entitled "Uveal Melanoma Exosomes Induce a Prometastatic Microenvironment through Macrophage Migration Inhibitory Factor," was co-authored by MediciNova’s collaborators Dr. Grazia Ambrosini, Research Scientist at The Herbert Irving Comprehensive Cancer Center (HICCC), Columbia University Medical Center; Alex J. Rai, PhD, Associate Professor of Pathology and Cell Biology, Columbia University Irving Medical Center; Richard D. Carvajal, MD, Associate Professor of Medicine at Columbia Vagelos College of Physicians and Surgeons and co-director of the Precision Oncology and Systems Biology research program at the HICCC; and Gary Schwartz, MD, Professor of Oncology at Vagelos College of Physicians and Surgeons, Division Chief of Hematology/Oncology at Columbia University Irving Medical Center, and Deputy Director at the HICCC.
The publication describes a preclinical study which characterized the proteomic content of uveal melanoma exosomes and identified the presence of markers with metastatic properties. The study included an evaluation of MN-166 (ibudilast) in a metastatic uveal melanoma model.
Key take-aways in the publication include:
Uveal melanoma exosomes (UM-exo) induce activation of cell signaling pathways and the release of cytokines and growth factors from hepatocytes. These exosome-stimulated liver cells could in turn induce migration of UM cells.
The proinflammatory cytokine macrophage migration inhibitory factor (MIF) was over expressed in UM exosomes and was a major player in these mechanisms. MIF blockade inhibited UM cell migration in co-cultures with exosome-stimulated hepatocytes and prevented the development of metastases in vivo.
Most inhibitors of hepatocyte-derived cytokines and growth factors had little or partial effects in blocking UM cell migration toward exosome-stimulated hepatocytes.
The MIF inhibitor MN-166 (ibudilast) dramatically inhibited UM cell migration (p<0.001), suggesting that MIF plays a major role in the cell-to-cell cross-talk.
In the metastatic UM mouse model study,
Quantified bioluminescence signal intensity in the abdominal region was dramatically reduced by MN-166 (ibudilast) treatment (p<0.05) in the metastatic UM mouse model at Day 46.
Histological analysis of the liver tissues of control mice showed the presence of tumor cell clusters, which were not present in the liver tissues of mice treated with MN-166 (ibudilast).
MN-166 (ibudilast) prevented metastasis in the metastatic UM mouse model.
This study provided the first in vivo evidence that MIF inhibition may serve as a novel adjuvant drug therapy to prevent metastasis in uveal melanoma.
MIF inhibition with MN-166 (ibudilast) may prevent metastatic spread in uveal melanoma patients and help to address the unmet critical need for novel and effective adjuvant therapies.
Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc. commented, "We are very pleased that the details of the research data regarding MN-166 preventing metastasis in the metastatic UM mouse model study has been published. Cancer metastasis is often the major driver of cancer-related death rather than the primary cancer. We previously reported that MN-166 reduced levels of immune suppressive myeloid-derived suppressor cells (MDSCs) and enhanced CD8 T cell activity in the tumor microenvironment. The data from this metastatic UM model study suggested that treatment with MN-166 can potentially address significant unmet medical needs for novel and effective therapies for patients with UM at risk of metastasis. We are optimistic that MN-166 could help patients with UM and other malignancies."
About MN-166 (ibudilast)
MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and for glioblastoma, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) is being evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS).