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'Smart' genetic therapy helps the body to heal itself

New approaches to genetic disease, based on cells' own ability to correct themselves, will be outlined today (Monday 8 May 2006) at the annual conference of the European Society of Human Genetics in Amsterdam, The Netherlands. Instead of replacing a faulty gene (commonly referred to as gene therapy) these new 'smart' approaches make use of the therapeutic potential that already exists in human biology.

Professor Brunhilde Wirth, from the Institute of Human Genetics, University of Cologne, Germany, will describe to the conference her team's work on developing therapies for patients with spinal muscular atrophy (SMA). This is a relatively common inherited disease in humans and the leading cause of death in infants, with an incidence of about 1 in every 6,000 newborns. Due to degeneration of the motor neurons in the spinal cord patients develop muscle weakness and atrophy of the legs, arms and trunk.

In patients with SMA the survival motor neuron genes (SMN1) is deleted, but they all carry a copy gene (SMN2). However, this only produces about 10% of the correct protein; insufficient to prevent the diseases. The severity of the SMA is influenced by the number of SMN2 genes, which normally vary between one and four ?the more copies there are the better the patient does.

Professor Wirth's team identified a drug ?valproate, used successfully in epilepsy treatment for decades ?that is able to increase SMN protein levels 2-4 fold in cell lines derived from SMA patients. Later, they showed that valproate also raised SMN levels in neuronal tissues such as cultured brain slices derived from epilepsy patients after surgery, as well as motor neuron cultures derived from rat embryos.

"The next step was to try this therapy in patients", said Professor Wirth. "In a first pilot trial, we enrolled ten parents of SMA patients who were treated with valproate for four months. We saw that valproate significantly increased SMN levels in blo
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Source:European Society of Human Genetics


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