Researchers Develop Mouse That Could Provide Advance Warning of Next Flu Pandemic

Researchers in Germany have developed a transgenic mouse that could help scientists identify new influenza virus strains with the potential to cause a global pandemic. The mouse is described in a study, “In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein,” that will be published April 10 in The Journal of Experimental Medicine.

Influenza A viruses can cause devastating pandemics when they are transmitted to humans from pigs, birds, or other animal species. To cross the species barrier and establish themselves in the human population, influenza strains must acquire mutations that allow them to evade components of the human immune system, including, perhaps, the innate immune protein MxA. This protein can protect cultured human cells from avian influenza viruses but is ineffective against strains that have acquired the ability to infect humans.

To investigate whether MxA provides a similar barrier to cross-species infection in vivo, Peter Staeheli and colleagues at the Institute of Virology, Medical Center University of Freiburg, created transgenic mice that express human, rather than mouse, MxA. Similar to the results obtained with cultured human cells, the transgenic mice were resistant to avian influenza viruses but susceptible to flu viruses of human origin.

MxA is thought to target influenza A by binding to the nucleoprotein that encapsulates the virus’ genome, and mutations in this nucleoprotein have been linked to the virus’ ability to infect human cells. Staeheli and colleagues found that an avian influenza virus engineered to contain these mutations was able to infect and cause disease in the transgenic mice expressing human MxA.

MxA is therefore a barrier against cross-species influenza A infection, but one that the virus can evade through a few mutations in its nucleoprotein. Staeheli and colleagues think that their transgenic mice could help monitor the potential dangers of emerging viral strains. “Our MxA-transgenic mouse can readily distinguish between MxA-sensitive influenza virus strains and virus strains that can evade MxA restriction and, consequently, possess a high pandemic potential in humans,” Staeheli says. “Such analyses could complement current risk assessment strategies of emerging influenza viruses, including viral genome sequencing and screening for alterations in known viral virulence genes.”

New Arsenal Against MRSA: New Study Reports Cannabinoids Effective Against Antibiotic-Resistant MRSA

Researchers have found that cannabinoid-based therapies have unique anti-bacterial properties that fight MSRA and other infectious bacteria. In vitro studies demonstrated that bactericidal synergy was achieved against multiple species of methicillin-resistant Staphylococcus aureus (MRSA) utilizing a proprietary cannabinoid-based therapeutic platform. MRSA species tested included community acquired- (CA-MRSA), healthcare-acquired- (HA-MRSA), and mupirocin-resistant (MR-MRSA) strains of MRSA.

Researchers also found that using unique strategic cannabinoid-based cocktails, fractional-inhibitory concentration (FIC) levels demonstrating synergy between mixtures of individual cannabinoid-based components ranged from 0.06 to 0.28. FIC findings below 0.5 indicate significant killing potential of the mixture. The work was led by NEMUS BIoscience, Inc. and the company’s discovery and research partner, the University of Mississippi (UM).

Dr. Mahmoud ElSohly, professor at the National Center for Natural Products Research (NCNPR) at the University of Mississippi commented: “Historically, many types of anti-infective compounds are derived from plants so to have a series of cannabinoid-related compounds exhibit activity against this dangerous pathogen is in keeping with prior efforts of drug development. I believe that these compounds, in addition to the bacterial killing capability, could also offer benefits associated with anti-inflammatory and anti-fibrotic properties that could enhance healing, especially against an organism associated with skin and soft tissue infections. The University, in conjunction with Nemus, is looking to expand the anti-infective capabilities of this series of compounds.”

Recently, the World Health Organization (WHO) placed MRSA on their list as one of the top six organisms that pose a global public health threat. “This anti-infective platform will constitute the NB3000 series of Nemus molecules and formulations.  While there are a number of compounds in the development pipeline against MRSA, we believe that this family of drug candidates could possess an excellent safety profile in addition to efficacy in neutralizing this bacterium,” stated Brian Murphy, M.D., C.E.O. and Chief Medical Officer of Nemus. “These unique botanically derived components establish an anti-infective platform which could potentially be expanded into other types of bacteria, as well as viruses, and fungi.”

The University of Mississippi, the state’s flagship institution, is among the elite group of R-1: Doctoral Universities – Highest Research Activity in the Carnegie Classification. The university has a long history of producing leaders in public service, academics, research and business. Its 15 academic divisions include a major-medical school, nationally recognized schools of accountancy, law and pharmacy, and an Honors College acclaimed for a blend of academic rigor, experiential learning and opportunities for community action.

Nemus will work with Dr. Elsohly, the University lead researcher on this project, to have this data submitted to a future scientific meeting and anticipates performing further testing against a variety of other bacterial species. Commercially, the company looks to actively pursue partnering opportunities for these candidate molecules. “This work highlights the importance of Nemus’ relationship with the University which has significant experience and intellectual capital related to cannabinoid chemistry and physiology, dating back to 1968,” added Dr. Murphy.

Nemus Bioscience is a biopharmaceutical company, headquartered in Costa Mesa, California, focused on the discovery, development, and commercialization of cannabinoid-based therapeutics for significant unmet medical needs in global markets. Utilizing certain proprietary technology licensed from the University of Mississippi, NEMUS is working to develop novel ways to deliver cannabinoid-based drugs for specific indications, with the aim of optimizing the clinical effects of such drugs, while limiting potential adverse events. NEMUS’s strategy is to explore the use of natural and synthetic compounds, alone or in combination with partners. The Company is led by a highly-qualified team of executives with decades of biopharmaceutical experience and significant background in early-stage drug development.

For more information, visit http://www.nemusbioscience.com.