A New Application for an Old Drug
A drug commonly used to treat osteoporosis is showing potential in the fight against flu.
The threat of a new influenza pandemic has emerged as one of the leading health concerns of the 21st century. But while pharmaceutical companies race to develop a successful vaccine, scholars at HKU are employing a distinctly Chinese approach to the problem.
The cross-disciplinary team, led by Chair Professor Lau Yu-lung, Doris Zimmern Professor in Community Child Health, and Dr Tu Wenwei of the Department of Paediatrics and Adolescent Medicine and Chair Professor Malik Peiris, Tam Wah-ching Professor in Medical Science, is researching ways to enhance the body’s own immune response to influenza.
Rather than attacking the virus directly, as most conventional drugs like Tamiflu do, their research is focusing on boosting the body’s innate immune system to effectively kill the virus. “There are two levels of immunity,” explains Professor Lau. “The first level we call innate immunity, which means you’re born with it, the second level is specific immunity, which means you have to learn from experiencing the infection and mounting a specific immune response.
“We thought that if we could somehow boost a patient’s innate immunity, then we might turn a nasty illness into a less severe one, we might turn a patient who could die from influenza into a patient who just has a mild infection and makes a full recovery. That is the whole premise of our research.”
One of the many arms of innate immunity is the gamma delta T-cell. These cells exist naturally in the blood and are known to fight viruses, like seasonal flu and its more deadly cousins H1N1, H9N2 and H5N1.
“So we thought that if we could somehow boost the level and function of gamma delta T-cells to a more active level then we might be able to fight the influenza virus better,” says Professor Lau.
This would also overcome the drawback inherent in antiviral drugs. As Type A flu viruses mutate continually antivirals have to be updated to keep apace with circulating virus strains. Additionally, novel antivirals can take years of trial and error in the laboratory before they come to market – not the most satisfying scenario in the event of a pandemic. Existing anti-flu drugs work mainly by targeting specific viral proteins, thereby blocking the replication and spread of the virus.
Fortuitously, a drug in common use for the treatment of osteoporosis is known to enhance the function and number of gamma delta T-cells in the body and should, in theory, be able to boost the body’s own immune response to flu through destroying the flu-infected cells, thereby limiting the viral production.
Phosphoantigens have been successfully used for decades to treat osteoporosis and have the potential to offer a ready-made and cost-effective solution to viral infections.
In a paper published in the Journal of Infectious Diseases, Professor Lau and his team showed that the application works in vitro. Early tests in mouse models are also showing promise.
“By activating the patient’s own immune system, the gamma delta T-cells destroy the cells infected by the virus and in doing so they are destroying the factory that produces the virus. So there will be no issue of the virus becoming resistant to the drug and the drug will not lose its potency because what it’s doing is trying to actually stop the virus from being produced.
“In a way, this is a uniquely Chinese approach – we are trying to boost the immune system rather than act directly against it.
“If the treatment is successful in the mouse model the third step will be designing a clinical study – that is if our hypothesis is accepted by the medical community, and if it is considered to be of some use.”
But what of the side effects? Reports that Tamiflu can cause nausea, insomnia and even psychiatric disorders in young people has left some patients understandably jittery about its potential benefits.
“In terms of the side effects of phosphoantigens, I think it’s a question of the risk-tobenefit ratio. All medicines have some risk but the beauty of using an old drug for a new use is that people are comfortable that indication, at length, in great detail for short and long term toxicity. If it has been used for a long time in a large number of humans then you are even able to document the very rare kind of side effects. These are the qualities that have encouraged us to go on and do these experiments.”