Australia is on the verge of becoming a pioneer in formulating a possible cure for chronic Hepatitis B infections and related complications, like cirrhosis and liver cancer. According to a recent press release, researchers from the Walter and Eliza Hall Institute in Melbourne have been recruiting patients for a phase 1 / 2 a clinical trial after a 100 percent positive response in pre-clinical trials. This treatment is at present one-of-a-kind, and these patients from Australia (Melbourne, Perth and Adelaide) and some from New Zealand (Auckland) are the first in the world to have the opportunity to test the new treatment. The chief scientists involved in this study are Dr. Marc Pellegrini, Dr. Greg Ebert and colleagues and their work has been published in the latest issue of the journal Proceedings of the National Academy of Sciences (dated 20th April, 2015).
So far, there has been no complete cure for chronic viral infections such as Hepatitis B. In these cases, the viral load is reduced considerably as a result of antiviral therapy, but the viruses become inactive and continue to reside within the host cells instead of getting eliminated from the hosts. Approximately 2 billion people are infected with HBV, with around 400 million cases of chronic infections being registered.
The study is being carried out in collaboration with Pennsylvania-based TetraLogic Pharmaceuticals. Their drug, Birinapant, is known for its efficiency in combating cancer cells and virus affected cells. Normally, when a virus attacks a cell, it transcribes and translates viral proteins and makes the host cell’s environment suitable for its own survival. The host cells have a self destructive mechanism which gets triggered once it is infected. This process is known as apoptosis. The virus produces proteins that can inhibit this process and keep the infected host cells alive. These proteins are known as Inhibitors of Apoptosis Proteins (IAPs). Birinapant destroys these IAPs and helps the host cells get rid of the virus, instead of targeting the virus directly.
The new study uses Birinapant in combination with the anti-viral drug entecavir, which reduced the viral load and helped in clearing the infection twice as faster, in preclinical models.
Explaining the mode of action of the drugs, Dr. Pellegrini said, “It is relatively easy for an organism to adapt to a drug, but it is very difficult to adapt to a change in the host cell. The virus relies on the survival mechanisms of the host, so if it can’t exploit them, it dies. Such a monumental change in the virus’ environment may be too big a hurdle for it to adapt to. Birinapant enabled the destruction of hepatitis B-infected liver cells while leaving normal cells unharmed. Excitingly, when birinapant was administered in combination with current antiviral drug entecavir, the infection was cleared twice as fast compared with birinapant alone. We are hopeful these promising results will be as successful in human clinical trials, which are currently underway in Melbourne, Perth and Adelaide.”
The preclinical trials gave way to human trials in December 2014, and patient recruitment has been conducted in collaboration with the Nucleus Network of hospitals across Australia and New Zealand.