Federal support for host-directed therapeutics will help prepare for future health emergencies

Trying to predict when avian flu will mutate and cross over to humans, when and where the next coronavirus variant will emerge, or if the Marburg virus (a close cousin of Ebola) will spread significantly beyond its origins in Equatorial Africa are difficult and costly endeavours. Proposals for preparedness range from daily monitoring of the world’s sewers to building vast, ever-growing catalogs of vaccine candidates that can be scaled up in a time of need. All worthwhile scientific endeavours perhaps, but not very practical. It’s too easy to guess wrong or miss a threat. Fortunately, a new class of host-directed therapeutics (HDT) could provide protection from both anticipated and unanticipated threats to our population. Such countermeasures can help modulate the body’s own immune response when confronted with novel infectious diseases, or even chemical agents. These HDTs could potentially reduce deaths, organ damage, shorten ICU stays (and free up hospital beds), and reduce financial costs in the system. Importantly, these therapies are designed to work across multiple infectious diseases and threats, and can be stockpiled pre-emptively ahead of outbreaks. Par Nijhawan is a physician and founder and CEO, Edesa Biotech, Inc. Photograph courtesy of Edesa Biotech This is particularly important in the context of biodefence, where the identity of the biological agent may not be immediately known, and there may be limited time to develop a targeted therapy. Another advantage of host-directed therapeutics is their potential to overcome drug resistance. As we saw during the pandemic, antimicrobial drugs can become less effective due to mutations and the emergence of drug-resistant strains of pathogens. Lastly, HDTs may be the only line of defence in severe cases when serious complications and death can result from the body’s overactive and dysregulated response to cell damage rather than the causal agent. Given the promise of HDTs for protecting both civilian and military populations, governments have increased funding for these transformative products and technologies to protect their populations from health security threats. In the United States, the Biomedical Advanced Research and Development Authority and Homeland Security are funding host-directed therapeutic candidates to expand their threat-agnostic portfolio of medical countermeasures. In Canada, the federal government has funded enabling research and clinical studies to develop threat-agnostic approaches for health security and to improve patient outcomes. The results are highly promising. Just this month, the University of Toronto published results from research funded by Innovation, Science and Economic Development Canada and Edesa Biotech, an Ontario-based company that I founded in 2015. Among the results, researchers demonstrated that multiple respiratory pathogens—Influenza A (H1N1), SARS-CoV2, human coronavirus, and H. influenzae—can cause overactive immune responses through a key immune receptor called TLR4, and that this overcharged response could be inhibited by a single host-directed therapeutic developed by Edesa. In addition to the pathogens tested in this research, a number of viral glycoproteins directly bind and activate TLR4, including those from Ebola virus, dengue virus, and respiratory syncytial virus. These findings underscore the opportunity for HDTs to target TLR4 modulation as a threat-agnostic therapy. The development of host-directed therapeutics needs government partnership and financial support if we are to be more fully prepared for health emergencies. Reducing the time to patient, building on our domestic bio-based economic capabilities, and stockpiling drugs that are effective and rapidly deployable for civilian and military use all require public-private partnerships. With continued support, particularly for Canadian researchers and Canadian biotechnology companies working in this space, HDTs have the potential to become an important tool in both pandemic preparedness and biodefence for Canada and our global partners. Par Nijhawan is a physician and pharmaceutical entrepreneur. Dr. Nijhawan is the founder and CEO, Edesa Biotech, Inc. Prior to Edesa, Dr. Nijhawan founded Medical Futures Inc., Digestive Health Clinic, and Exzell Pharma. He received his MD from the University of Ottawa, and completed his internship at Yale University and his internal medicine residency and gastroenterology fellowship at the Mayo Clinic. The Hill Times