Programme : Back to Prof Alan Morgan
Poster
29

Using nematode worm models of human neurological diseases to identify novel therapeutic drugs and mechanisms of action.

Discussion

Epilepsy affects 1% of the population and around a third of patients are resistant to current antiepileptic drugs. Neurodegenerative disorders such as Alzheimer’s disease affect one in six 80-year-olds and cost the UK over £20 billion per year. The existing drugs for both conditions merely provide symptomatic relief and do not impact on the underlying disease process. Therefore there is a pressing need to identify novel drug therapies that inhibit disease progression and to understand their molecular targets and mechanisms of action. Our approach is to create nematode worm models of these neurological conditions by mutating the worm orthologues of genes that have been shown to harbour disease-causing mutations. These simple animals can then be used for phenotypic screening to identify potential novel therapeutics; and for chemical genetic studies to systematically identify drug mechanisms of action. Here we show data on a worm model of epileptic encephalopathy caused by mutation in the human GABRB3 gene; and of the neurodegenerative disease adult onset neuronal lipofuscinosis (ANCL) caused by mutations in the human DNAJC5 gene. Our data show how these worm models can be used to identify novel therapeutic compounds and provide insight into molecular targets of existing drugs. Given the high costs and ethical implications of conventional mouse models of neurological diseases, the worm models described here may offer an attractive alternative drug discovery model.
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