My creative invention was the discovery and development of a new therapy to treat, and potentially eliminate, chronic hepatitis B virus (HBV) infection. I used the clinical stage drug ‘birinapant’ to specifically kill HBV infected liver cells by initiating a self-destruct signal in the host cells. Only infected cells are susceptible to this mode of killing. This is a completely novel innovation in the treatment of infectious diseases. My therapy cured HBV infection in preclinical models - something that has never been achieved before and this newly developed treatment is now in clinical trials. I am currently translating this breakthrough to the treatment of other overwhelming and chronic infectious diseases such as HIV infection and tuberculosis.
Infectious diseases, collectively, cause more deaths and suffering than any other single disease. HBV alone has infected more than 2 billion people globally, including over 230,000 Australians. Chronic HBV infection causes liver cirrhosis and liver cancer, which is now the second leading cause of cancer related deaths. Currently, there is no cure for HBV infection. Standard therapies directly target the virus and reduce its capacity to replicate, but they never fully eliminate virus and hence the drugs must be taken lifelong. A cure is urgently required to mitigate the death and illness caused by chronic HBV infection.
I discovered that the drug ‘birinapant’ causes HBV infected liver cells to commit suicide, but it does not harm uninfected cells. This altruistic death of infected cells removes the reservoir of infection and completely eliminates virus in preclinical studies. I published this work in May 2015 and described the novel mechanism of action in two back-to-back papers [1,2]. My discovery progressed to Australian HBV clinical trials this year and the trial will expand into Asia in 2016 . I am now translating this new and paradigm-shifting therapy  to treat other infections with high morbidity and mortality, such as HIV and tuberculosis (TB) that cause approximately 4 million deaths each year.
HIV and TB can hide and remain dormant in cells and then reactivate at anytime to cause disease. Accumulating data indicates that my treatment can preferentially kill these latently infected cells and prevent disease relapse. One third of the world’s population is latently infected with TB. People with dormant TB who receive immune suppressing drugs, such as those used to treat rheumatoid arthritis, can reactivate their infection and develop severe disease. My great hope is that the therapy I discovered is the “killer cure“ for many infections, including those caused by microbes that try to hide.
3. Additional Details
- Ebert G. et al., Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus. Proc Natl Acad Sci USA. 2015 May 5;112(18):5797-802. doi: 10.1073/pnas.1502390112.
- Ebert G. et al., Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci USA. 2015 May 5;112(18):5803-8. doi: 10.1073/pnas.1502400112.
- Lucifora J, Trepo C., Hepatitis: After HCV cure, HBV cure? Nat Rev Gastroenterol Hepatol. 2015 Jul;12(7):376-8. doi: 10.1038/nrgastro.2015.103.