Brain Discovery Raises Epilepsy Drug Hopes

Researchers at the Heart Research Institute have discovered a brain chemical that protects people with epilepsy from deadly heart problems.

This work paves the way for exciting new protective drugs. The important new study reveals significant links between epilepsy, heart disorders and the immune system that could change the way the brain condition is treated.

“We’ve discovered that a helpful brain neurotransmitter called PACAP, plays a soothing role in the brain during epilepsy; too little PACAP can make seizures worse, while too much glutamate – another brain chemical – can also make seizures worse,” says Professor Paul Pilowsky, lead investigator of two studies published in the prestigious Journal of Neuroscience, which is the Journal of the United States Society for Neuroscience.

“Armed with this knowledge, we expect that drugs that target these chemical neurotransmitters, will protect people with epilepsy from the risk of sudden unexplained death.”

Epilepsy is the world's most common serious brain disorder, with 50 million people experiencing it globally at any given time. 

More than 250,000 Australians are living with the condition, and up to 3.5 per cent of the population will be diagnosed with it at some stage in their life.

Sufferers tend to experience recurrent seizures, a disturbance in the electrical activity of the brain that can be severe and disabling. The condition disturbs the nervous systems which controls breathing, causing tongue biting and loss of consciousness. But it can also spark cardiac changes, namely an abnormal heart beat or arrhythmia that can be dangerous.

“These arrhythmias seem to be linked to a syndrome called sudden death in epilepsy, the most common cause of death in epilepsy sufferers,” says Professor Pilowsky, who himself has epilepsy. “While rare, the syndrome is poorly understood and can’t be prevented, an unsettling truth that those with epilepsy must live with.”

Professor Pilowsky and his team in HRI’s High Blood Pressure Research Group work to shed light on the mystery by investigating the role of brain chemicals in causing these cardiovascular changes.

They looked closely at glutamate, PACAP and many other brain chemicals to determine their role in controlling the cardiovascular system.  It is expected that interfering with or enhancing the activity of these neurotransmitters that normally play a soothing role in the brain during epilepsy by activating brain immune cells, called microglia, will help to prevent abnormal heart rhythms and death during epileptic seizures.

“Because we found that during an epileptic seizure, blocking the action of PACAP made the seizure worse, we think that PACAP plays a vital role in epilepsy, and that by enhancing its action we might be able to treat a problem that is claiming lives.”

Taken together, the HRI’s findings illuminate the complex relationship between neurons, the immune system and disorders such as epilepsy, Professor Pilowsky says.

The work, which features on the cover of the international journal’s January issue, paves the way for the development of medications that enhance the actions of this transmitter.

“It’s still early days but in the future we anticipate that this work will lead to new treatments for disorders like epilepsy where the normal relationship between neurons and the brain’s immune system breaks down,” he says. It is important to note that epilepsy is only one of many disorders now thought to be affected by the immune system, including hypertension and many degenerative disorders.

“To be able to offer a therapy for a condition with sometimes fatal consequences would obviously bring huge relief to millions of people affected worldwide.”

About Epilepsy
  • About 50 million people globally have epilepsy at any given time, with 2.4 million diagnosed every year, according to the World Health Organisation.
  • In Australia, over 250,000 Australians are living with epilepsy, and more than 800,000 people will be diagnosed with the disease at some stage in life, according to Epilepsy Action Australia.
  • People with epilepsy tend to suffer seizures, where the normal electrochemical activity of the brain is disrupted
  • Anyone can be affected by seizures at any age, but epilepsy is most frequently diagnosed in infancy, childhood, adolescence and old age, and it can be outgrown
  • Sufferers are at risk of sudden unexpected death, particularly if their seizures are frequent and poorly controlled
  • The cause of this sudden death is a mystery but current research suggests respiratory or cardiac dysfunction may be to blame
  • Heart Research Institute researchers have identified a transmitter in the brain that, when blocked, triggers abnormal heart beats or arrhythmias linked to sudden death
  • By targeting this transmitter, scientists could develop new drugs the protect sufferers from cardiac dysfunction and sudden death

 

This ran as an exclusive story on 7 News, May 22nd, 8:49 pm

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