29 Jun 2011

Influenza is an acute respiratory virus infection associated with significant morbidity and mortality. It further threatens global public health as some strains of influenza are resistant to currently available antiviral agents. Researchers at The University of Hong Kong (HKU) Li Ka Shing Faculty of Medicine discovers that pamidronate, a drug well established for treatment of bone diseases, can effectively control influenza diseases caused by seasonal, pandemic H1N1 or avian H5N1 influenza virus by boosting one of the first line of the host immune defense, i.e. human gamma-delta T cell (γδ-T cell) immunity. The novel therapeutic option has been proved effective for all the strains of influenza viruses tested in a humanized mouse model that contains a complete human immune system. The result of this study has just been published in the prestigious scientific journal - Journal of Experimental Medicine.

Results of the study
HKU is one of the very few laboratories worldwide to have successfully established the "humanized mouse" model, in which the mice contain the complete human immune system. Through this humanized mouse model, HKU researchers finds that pamidronate, an old drug for treatment of osteoporosis and Paget’s disease, can reduce influenza disease severity and mortality, inhibit influenza virus replication and prevent inflammation in lung through boosting the immunity of human gamma-delta T cells, a subset of white blood cells. This treatment can control diseases caused by all the strains of influenza viruses tested, including human type A seasonal influenza viruses (H1N1 and H3N2), pandemic influenza virus (swine influenza virus H1N1), avian influenza virus (H5N1) and type B influenza virus. This research is at pre-clinical stage and now will be expanded to human clinical trials.

Background of the study
Vaccines may not be available in time for a novel pandemic strain, e.g. pandemic H1N1 virus and antivirals are the important front-line for defense against such threats. At present, the options for antiviral therapy are limited. Some strains of influenza are resistant to currently available antiviral agents. Furthermore, the response of severe H5N1 influenza disease to currently available antivirals is sub-optimal. Thus, there is an urgent need to develop alternative strategies for treating influenza.

Conventional antiviral drugs for influenza target the action of viral proteins allowing the virus the possibility to escape their effect by mutation of the genes encoding for the relevant viral protein. Enhancing the body’s immune response, i.e. gamma-delta T cells in this study, broadly against many influenza viruses simultaneously is an alternative strategy that does not allow the virus to escape by mutation.

Significance of findings
Firstly pamidronate has been commonly used for the treatment of osteoporosis and Paget’s disease for over 20 years and is known to be safe. Therefore, this "new application of an old drug" potentially offers a ready and cost-effective solution to influenza virus infections.

Secondly, studies in animals may not always reflect the situation in humans and therefore it may not be possible to directly translate biomedical findings from animals to humans. But HKU used the "humanized mouse" model in this study which has reduced the gap between the mice and humans and provided a powerful and low-cost platform for preclinical study of drugs such as pamidronate. It provides an ideal model in therapeutic studies of human pathogens related to infectious diseases, for vaccine testing and stem cell studies.

About the research team
The research is led by Dr Tu Wenwei, Associate Professor, and Professor Lau Yu-lung, Doris Zimmen Professor in Community Child Health and Head of the Department of Paediatrics and Adolescent Medicine, and Professor Malik Peiris, Tam Wah-ching Professor in Medical Science of the Department of Microbiology of The University of Hong Kong Li Ka Shing Faculty of Medicine.

Acknowledgement
This study was supported in part by the Area of Excellence programme on Influenza supported by the University Grants Committee of the Hong Kong SAR, China (Project No AoE/M-12/06); Research Fund for the Control of Infectious Diseases, Hong Kong SAR government (07060482); General Research Fund, Research Grants Council of Hong Kong (HKU 777108M, HKU777407, HKU768108).

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