Photo: Novateur Ventures
A novel strategy has been developed by Novateur Ventures, which provides new hope in the battle against COVID-19. The study titled ‘A Novel Strategy to Mitigate the Hyperinflammatory Response to COVID-19 by Targeting Leukotrienes’ was published in Frontiers in Pharmacology, a leading peer-reviewed journal.
The strategy co-authored by Ali Ardakani, Founder & Managing Director at Novateur Ventures, and Dr. Colin D. Funk (Queen's University, Kingston) analyzes lipid mediators, known as leukotrienes, as the cause for hyperinflammatory response manifested in severe COVID-19 cases. Patients with severe COVID-19 develop an overwhelming state of inflammation with multi-organ dysfunction and leukotrienes have been overlooked.
“Globally the race to develop new therapeutics or repurpose existing drugs to cultivate an effective therapeutic treatment for COVID- 19 is urgent. At Novateur, our research has been well underway since the first cases were discovered,” says Ardakani. “I am very pleased today to announce a strategy we believe can potentially impact COVID-19 patients in a safe and effective manner.”
Since Novateur began their in-depth studies, only two treatments (remdesivir, dexamethasone) have demonstrated modest ability to reduce disease progression and severity; however, there is still a high unmet need for additional improvement. Leukotrienes have some of the most potent impacts on immune cell trafficking and vascular leakage in biological systems, two important steps that take place in COVID-19. Novateur’s research proposes a simple treatment paradigm using two generic drugs, normally directed to blocking inflammation in airways of patients with asthma, to target the hyper-inflammatory response insevere COVID-19. This will be accomplished by a combination of a leukotriene biosynthesis blocker zileuton (Zyflo® controlled release formulation) and an inhibitor of the cysteinyl leukotriene 1 receptor montelukast (Singulair®). Both these agents, now generic, have been on the market for many years, and their activity and side effects in humans are well known.
In COVID-19, providing zileuton/montelukast combination prior to out-of-control host inflammatory cell recruitment to the lungs and before pulmonary edema sets in is paramount. Initiation of treatment with zileuton/montelukast should take place early on, shortly after a positive test is confirmed and before major symptoms arise. Currently it remains very difficult to predict which patients will progress to severe COVID-19 disease. The standard of care is basically symptomatic control (i.e. acetaminophen for fever and muscle pain) and observation. The proposed zileuton/montelukast combination could readily be added in this setting, with the goal to switch off the hyper-inflammatory response. The incentive to move forward quickly is vital to combat COVID-19 while waiting for a preventative vaccine or other treatments.
“Our journey studying COVID-19 and potential therapeutics is still at an early stage. We hope that our proposed treatment plan can effectively stop COVID-19 from becoming a life-threatening disorder,” says Funk, a key leader in the leukotriene field. “Novateur will continue to concentrate its efforts on this global pandemic that has claimed the lives of so many. It is important to recognize the sharing of critical data and the very collaborative approach this fight has taken. We are working diligently with unprecedented speed to move a clinical trial forward as quickly as possible in the USA where cases of COVID-19 are high.”