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News Archive 2012
Delivering Sweet Solutions for Brain Disorders

Picture: Professor Caitríona O'Driscoll, Professor John F Cryan and PhD student Bruno Godinho
UCC researchers have developed an innovative strategy to deliver a therapy that successfully silences a gene responsible for the neurodegenerative condition known as Huntington’s Disease (HD).
Brain disorders affect approximately 30% of the Irish population annually with immense personal, social and economic costs.
There are two major challenges in developing therapeutic strategies for the brain. Firstly, the blood brain barrier keeps most medicines out of the brain, secondly brain cells (neurons) themselves are very difficult to penetrate in a safe manner. In tackling this later problem scientists at the School of Pharmacy and Department of Anatomy and Neuroscience at UCC have come up with an innovative strategy to deliver a therapy that successfully silences a gene responsible for the neurodegenerative disease Huntington’s Disease (HD).
Huntington’s Disease is caused by a defect in a gene called Huntingtin (HTT) that results in the accumulation of a toxic HTT protein within the brain. As a consequence nerve cells within the brain die and lead to a broad range of symptoms, most notably involuntary rapid movements. Although HD is a rare disease estimated to affect 10 people in 100,000, HD brings an enormous burden to the patient’s quality of life and the disease does not “skip generations”.
Professor Caitriona O’Driscoll (Pharmacodelivery group in School of Pharmacy, UCC) and her long standing collaborator Dr Raphael Darcy (University College Dublin) have developed sugar-based carriers called cyclodextrins which are able to encapsulate and transport molecules which silence the expression of toxic genes. In collaboration with neuroscientist Professor John F Cryan (Department of Anatomy and Neuroscience, UCC) and through the efforts of PhD student Bruno Godinho the application of this novel technology to brain disorders was made possible. They have shown that these sugar-based carriers effectively deliver silencing molecules (siRNAs) into nerve cells reducing the levels of the toxic HTT protein. Furthermore, the results obtained in cell-based models also translated to mice. Reducing the HTT messages by direct administration into the brain of a mouse model of HD resulted in alleviation of some of the motor deficits.
“This is a very encouraging breakthrough for disorders where there is often very little hope,” says Professor Cryan. “We now have an effective and non-toxic carrier which could be applied to many brain disorders especially those with genetic basis. However”, he cautions “whilst these experiments in cells and model systems are encouraging, we are still a long way from transferring this technology to human use.”
The study has recently been published online in the journal Molecular Pharmaceutics.