Therapy ‘silences’ gene responsible for Huntington’s

Researchers at University College Cork have developed an innovative strategy to deliver a therapy that “silences” a gene responsible for the neurodegenerative condition known as Huntington’s disease.

Huntington’s disease is a hereditary neurological disorder that causes brain cell degeneration, leading to deterioration of the physical, cognitive, and emotional self.

Symptoms usually appear between the ages of 30 and 45, although they may appear earlier or later.

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 difficult to penetrate in a safe manner.

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 Huntington’s.

Huntington’s disease is caused by a defect in a gene called Huntington (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 Huntington’s disease is rare and estimated to affect 10 people in 100,000, it can bring an enormous burden to the patient’s quality of life and it does not “skip a generation”.

Professor Caitriona O’Driscoll of the pharmacodelivery group in the school of pharmacy, UCC, and her long-standing collaborator, Dr Raphael Darcy of 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 of UCC’s department of anatomy and neuroscience, the application of this technology to brain disorders was made possible.

They have shown that these sugar-based carriers effectively deliver silencing molecules in to 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 Huntington’s disease resulted in alleviation of some of the motor deficits.

“This is a very encouraging breakthrough for disorders where there is often very little hope,” said Prof 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 said while “these experiments in cells and model systems are encouraging, we are still a long way from transferring this technology to human use”.


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