Australian Scientist Recognised for Ground Breaking Work: Unlocking the Genetic Mystery Surrounding Epilepsy
The work of an Australian scientist and his team in discovering the first ever epilepsy gene has been recognised in the awarding of the 2002 GlaxoSmithKline Australia Award for Research Excellence.
While historically it was widely believed heredity played a significant role in the development of epilepsy, Professor Samuel Berkovic, Director of the Epilepsy Research Institute at the Austin and Repatriation Medical Centre in Melbourne, has lead his team in identifying the first known gene for the condition, offering new hope for improved diagnosis and management. Epilepsy affects approximately 2 per cent of Australians at some time in their lives.
By using a large family study to track genetic mutations the Australian team was able to identify the first genetic marker for a rare form of epilepsy known as autosomal nocturnal frontal lobe epilepsy (ADNFLE). The condition is particularly frightening, as unlike other epileptic seizures, the sufferer remains semi-aware during the attack.
The discovery ensured Australia became recognised as world leaders in the area of epilepsy research. In the seven years since, the Australian team (which includes Professor Berkovic's team in Melbourne and Professor Grant Sutherland and Associate Professor John Mulley's teams from the Molecular Genetic Unit at the Women's and Children's Hospital in Adelaide) have been involved in the discovery of eight of the 11 genes now known to be associated with the condition. The unique combination of the clinical and molecular genetics expertise has been responsible for elevating the team to the status of undisputed leaders in this field.
The Research – Revolutionising Our Understanding of Epilepsy
Having been inspired to pursue epilepsy research by colleagues at the Austin Centre in the early 1980's, it wasn't until 1987 that Professor Berkovic, after returning from a fellowship position at the Montreal Neurological Institute USA, began to lead Australian efforts into epilepsy research.
Motivated by a strong belief that to be successful Australian researchers needed to use their imagination to come up with novel and unique research models, Professor Berkovic initially focused on epilepsy in twins. Using the NH&MRC Twin Registry he has identified over 500 sets of twins with seizures which has led to a deeper understanding of the clinical genetics of epilepsy. An important source of insight into the condition, the Registry continues to be a constant source of new ideas for future research.
As the molecular genetics revolution began, Professor Berkovic and his team set out to identify the genes involved in the so-called idiopathic epilepsies – epilepsies with no known physical or environmental causes such as brain injury. To this end, the team moved into large family studies.
It took over 18 months to meticulously track the ADNFLE disorder through one South Australian family. A year later the team had identified the gene and tracked it to chromosome 20. The team then linked the mutation to a subunit of the neuronal nicotine acetylcholine (ACH) receptor. The groundbreaking discovery was published in Nature Genetics in 1995. Not long after, the team were also credited with discovering the genetic marker for another condition called generalised epilepsy with febrile seizures plus (GEFS-+).
Combined, these two findings provided major insight into the condition and enabled basic biological research to follow.
The Implications: Identifying Genes Opens Doors to Better Diagnosis and Treatment
Professor Berkovic believes one of the most significant implications of his research is the proof that the role of perinatal injuries in the development of epilepsy has been grossly exaggerated and that, in fact, genetic factors play a role in a least half of all patients with epilepsy. This seemingly simple insight creates two main opportunities for future management: enhanced diagnosis and improved treatment.
"I have no doubt these discoveries will soon become part of routine clinical diagnosis. This will enable us to rapidly screen for the condition and thereby improve disease management," said Professor Berkovic.
According to Professor Berkovic, the opportunities for the development of improved treatments are perhaps even more important.
"Virtually all of the anti-epileptic drugs currently available have been discovered by chance. They have been screened against a variety of animal models that allegedly reproduce the human condition," he said.
"We have been in desperate need of new systems to test drugs for novel modes of action against epilepsy. There can be no better way than having the fundamental defect identified and modelling it in simple laboratory systems and animals. This will enable us to develop new compounds that will confer obvious and significant benefits."
Recognition: The GSK Award for Research Excellence
Awarded annually in recognition of distinguished discoveries in scientific and medical research that lead to demonstrated or potential benefit to human health, a requirement of the GlaxoSmithKline Award for Research Excellence is that the majority of the research is undertaken in Australia. Recipients receive an honorarium of $30,000 to acknowledge their discovery and contribution to science and help further their work. Today the Award is regarded as on of the most prestigious within the Australian Research Community.
According to Professor Berkovic what is particularly pleasing about receiving the prestigious Award is the fact that his group is principally a clinical research group.
"Clinical research is sometimes put down as people believe doctors can't really do research and run a practice. While it is a difficult balance, hopefully this Award provides evidence that it can sometimes work," said Professor Berkovic.
Speaking at the Award presentation dinner in Melbourne on Wednesday 30th October, Dr Tachi Yamada, Chairman of Research and Development for GSK, congratulated Professor Berkovic on his persistence in the pursuit of greater understanding of this perplexing condition.
"Professor Berkovic and his team have made a most important discovery which offers unique opportunities to enhance treatment for epilepsy. For this we commend Professor Berkovic," said Dr Yamada.
Commenting further, Mr Daniel Tasse, Managing Director, GlaxoSmithKline Australia, said Professor Berkovic's commitment to collaboration reflected GlaxoSmithKline's commitment to supporting innovation, research and development in Australia.
"Developing Australia's knowledge base and supporting our scientists is critical to our ability to offer world class research and science capabilities into the future. The GlaxoSmithKline Australia Award for Research Excellence rewards Australian scientists by recognising their contribution to science and investing in their work.
"There is no doubt that the groundbreaking work of Professor Berkovic and his team has contributed substantially to our understanding of epilepsy and I congratulate him on winning this prestigious award," Mr Tasse said.