Professor Christopher M. Overall, Chief Scientific Officer
InterfeRx is a spin off company in the Life Sciences Centre, UBC whose mission is to develop and bring to clinical trial novel broad-spectrum anti-viral drugs.
The foundation of InterfeRx is our Intellectual Property based on our exciting finding that a secreted metalloproteinase from macrophages targets viral infected cells, crossing the plasma membrane and nuclear envelope and functioning thereafter as a transcription factor (Marchant et al. 2014, Nature Medicine). Unexpectedly, MMP12 bound a specific sequence in the promoter of IkBα and turned on gene transcription. This was essential for secretion of the anti-viral protein Interferon-α. Mice deficient in MMP12 died of virus infection. Thus MMP12 inside the cell is protective. However, MMP12 also had a homeostatic role in the extracellular environment. Outside the cell MMP12 was identified as the primary enzyme that clears Interferon-α from plasma and infected tissues. This removes the antiviral protective factor.
We developed a novel compound that was a selective MMP12 inhibitor in order to stabilise Interferon-α and increase life-saving Interferon-α levels in the plasma and tissues. With key chemical modifications to the structure of the inhibitor we prevent MMP12 crossing through the cell membrane and so preserved the life-saving antiviral intracellular functions of MMP12. Virus infected mice treated with the InterfeRx antiviral drug showed a dramatic increase in systemic Interferon-α levels, that was associated with the elimination of viral replication in infected tissues and with a marked decrease in viral load.
Thus, the mission of InterfeRx is to bring this broad-spectrum anti-viral compound to human clinical trials .
References
Marchant, D.J., Bellac, C., Moraes, T.J., Wadsworth, S.J., Dufour, A., Butler, G.S., Bilawchuk, L.M., Hendry, R.G., Robertson, A.G., Cheung, C.T., Ng, J., Ang, L., Luo, Z., Heilbron, K., Norris, M.J., Duan, W., Bucyk, T., Karpov, A., Devel, L., Georgiadis, D., Hegele, R.G., Luo, H., Granville, D.J., Dive, V., McManus, B.M., and Overall, C.M. 2014. A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity. Nature Medicine 20, 493-502. doi 1038/nm.3508.
