A medication used in World War II as an antidiuretic is one of two drugs Melbourne researchers believe could reduce the number of people who die from the flu yearly. Influenza cases surged Australia-wide in 2019, and the death toll has climbed to about 300 in a season described as “brutal”. A two-year-old boy in WA is thought to have died from the virus, and teenagers believed to be perfectly healthy have died after getting the flu. The flu vaccination can prevent people from getting sick, but until now, little has existed to help sufferers in the middle of severe and potentially fatal virus cases.
Researchers at Melbourne’s Hudson Institute of Medical Research have identified two drugs — the antidiuretic Probenecid and an anti-arthritis medication — that could change that. “The potential for these drugs is enormous. There is a massive worldwide global health burden for influenza infections,” scientist Ashley Mansell said. “And therefore, the applications are huge and have a massive capacity to make a real difference to health outcomes, particularly to the flu, across the world.” The Hudson Institute has spent the past decade looking at reducing over-inflammation in the host rather than how to attack the virus, which is becoming increasingly resistant to drugs.
The flu can kill in several ways, but over-inflammation is the primary culprit. “Inflammation is our friend; inflammation is good, but sometimes it becomes too much. That causes tissue damage, which can cause lethality,” Associate Professor Mansell said. The drugs could dampen inflammation symptoms such as fever, chills, swelling, joint pain, and redness, which the researchers hope could save lives.
Medicines could answer to ‘mutating’ flu.
Probenecid was developed in the 1940s and used during World War II to prolong the life of penicillin and is now used to treat gout. Researcher Michelle Tate said the drug had a “perfect safety profile” after being used for decades. The second drug identified by the institute as a potential weapon against flu deaths is kZ11645373, which has been clinically trialed fto treat arthritis. In findings published in the British Journal of Pharmacology today, the scientists said both drugs target a molecule — the ATP receptor P2X7 — that plays a key role in inducing inflammation.
Associate Professor Mansell said the flu had become “very smart” and “mutates at an excessive rate,” so anti-viral medication had become less effective in prevention. The research suggests how the drugs interact with the immune system to slow inflammation could save people’s lives once they contract severe cases of influenza. Dr. Tate, who authored the journal report, said these drugs already exist and greatly boosted the research and development phase. “We could re-purpose them for the flu much quicker than if we were to design a new drug,” she said.
It could be years before the drugs are available to treat influenza, and the team needs to confirm how they would be administered to flu patients. The institute is now trying to collaborate with other health authorities for clinical trials to treat Avian flu and other severe influenza infections. Associate Professor Mansell said the P2X7 molecule was involved in other illnesses, and the drugs could also be used to treat other health problems. “Infectious disease, what we call sterile diseases, things like gout and cancer, has been implicated in. And therefore, these drugs may have applications further than just actually treating the flu,” he said.
