MediciNova Announces Publication of MN-166 (ibudilast) Data regarding Prevention of Metastasis in Uveal Melanoma in Molecular Cancer Research
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 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.
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).
Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund
Source: MediciNova, Inc.
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