Hope for Hepatitis B sufferers
Wits University
 Chronic infection with hepatitis B virus (HBV) is endemic to sub-Saharan
Africa, parts of east Asia and the western Pacific islands. According to the
World Health Organization, 2 billion people have been infected with HBV and
there are more than 350 million people who fail to eliminate the virus and as a
result become chronic carriers; as many as 40% of these individuals will develop
liver cancer and/or cirrhosis as fatal complications.
Chronic HBV infection is the ninth leading cause of death worldwide,
accounting for 1.2 million deaths annually. Despite the availability of
effective HBV vaccines for several years, the number of people in the world who
are infected has not decreased significantly. South Africa is one of the few
African countries which, in 1995, made the vaccine compulsory for children.
Current treatment of HBV, which may have side effects such as flu-like
symptoms are largely ineffective, particularly in sub Saharan carriers of the
virus. Novel approaches to treatment are an urgent global medical objective,
says Dr Patrick Arbuthnot of Wits University in South Africa. Arbuthnot and
postgraduate students Marc Weinberg and Marc Passman have been at the coalface
of developing a cure for hepatitis B using therapeutic ribozymes.
Therapeutic ribozymes are a novel class of drugs that have shown promise in
treating a variety of diseases, including HIV. They are RNA molecules that
behave as enzymes or "molecular scissors", and typically catalyse
reactions that result in the specific cutting of a different target RNA
molecule.
Using modern techniques of biotechnology, ribozymes can be designed to
recognise, bind to, and cut any disease-causing RNA, such as HBV RNA. Suitably
designed therapeutic ribozymes inhibit HBV replication by inhibiting reverse
transcription of viral RNA and also indirectly by blocking the production of
proteins that are critical for virus propagation.
Arbuthnot and team have patented a ribozyme gene therapy application, which
has been shown in cell culture models of HBV infection to block the replication
of the virus. These ribozymes inhibit the function of an important viral protein
that is required for viral infection and is thought to play a pivotal role in
the development of liver cancer in chronic carriers of HBV.
The clinical application of anti-HBV ribozymes requires that these agents be
delivered efficiently to HBV-infected liver cells. Their approach is to use
carrier molecules called liposomes, which are small, spherical fatty membranes.
They encapsulate the ribozyme genes, and ensure that they are protected from
degradation and are efficiently delivered to the liver. The team aim to perform
trials in animals that are naturally infected with HBV-like viruses. Their hope
is that these molecules will be without the side-effects of conventional HBV
treatment and will prove to be safe and effective antiviral agents for use in
humans.
Arbuthnot envisages that the treatment which will be given by injection over an estimated 6 month period will be fairly affordable. Arbuthnot has recently
won a R9.1 million grant over the next three years from the Department of Arts,
Culture, Science and Technology's Innovation Fund, which is administered by the
National Research Foundation (NRF) to develop the ribozyme therapy. He states
that it may be at least five years before this is a treatment reality.
|
