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Gene therapy may help epilepsy patients

11 October 2004

Gene therapy may help epilepsy patients

A novel gene therapy strategy may help reduce seizures in adults suffering from epilepsy according to a University of Auckland PhD student.

Deborah Lin, from the Faculty of Medical and Health Sciences, is investigating the effects of a therapeutic gene transfer in a particular form of epilepsy which affects the brain's temporal lobe region.

Temporal lobe epilepsy (TLE) is characterised by epileptic seizures originating from and involving mainly the temporal lobe of the brain.

There is a high incidence of TLE in adults and it is resistant to drug therapy despite the many anti-epileptic drugs developed in recent years.

"Epileptic seizures inhibit the quality of daily life. I'm looking at the causes of seizures and how they can be addressed.

"A seizure is an imbalance between a person's excitatory and inhibitory drives in the brain. Treatments that decrease excitation or increase inhibition may be effective in impeding seizure development."

Gene therapy has generated enormous scientific, medical and public interest over the last decade. While some 1000 clinical protocols involving gene transfer have been presented, relatively few have been for neurological diseases and none, so far, has focused on epilepsy.

"Research suggests that the proteins neuropeptide Y (NPY) and galanin (GAL), which are naturally found in the brain, can help reduce seizures. Increasing the level of these proteins through gene transfer provides an excellent opportunity to help epilepsy patients.

"Gene therapy with the particular delivery system we have chosen is safe and has been well tested in laboratories. It is localised, which means that we only inject the therapeutic genes in the area where the seizure originates, thus reducing the risk and impact of any side effects," says Deborah.

Earlier this year, Deborah undertook a pilot study involving lab models under the supervision of Professor Matthew During and Dr Debbie Young.

Results so far have been promising and led to publications in the internationally prestigious journals, European Journal of Neuroscience and the Journal of Neuroscience.

"Gene transfer enabled the production of specific anticonvulsant proteins in the brain which effectively helped to curb the seizures. Our data to date shows that seizures are reduced by approximately 50-75 percent.

"The results are significant because the data is some of the first to demonstrate the potential and feasibility of targeted gene transfer as a novel therapeutic strategy for drug resistant temporal lobe epilepsy."

Deborah and her supervisors are now working closely with researchers in US, Italy, Austria, Australia and Brazil to undertake further pre-clinical trials. Once the data is validated by definitive preclinical efficacy and toxicity studies, the next step is clinical trials for humans.

"Gene therapy has provided families and clinicians with hope and a new treatment approach in the management of epilepsy. However, there are still questions that must be answered before we can trial this treatment in human beings.

"This research has brought us a significant step closer to developing a treatment for those patients for whom drugs don't work. With gene therapy the benefits are long-term you don't have to take drugs every day," says Deborah.

Deborah's study is partially funded by the Health Research Council of New Zealand.


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