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Huntington's protein is 'super assassin' for cancer cells

19 February 2018
Appeared in BioNews 938

Researchers have discovered that the protein responsible for the development of Huntington's disease is highly toxic to cancer cells. While the molecule has been understood in the context of Huntington's disease for years, it has only recently been found to have treatment implications for other diseases.

'This molecule is a super assassin against all tumour cells,' said senior author Dr Marcus Peter at Northwestern University Feinberg School of Medicine in Chicago, Illinois. 'We've never seen anything this powerful.' The study was published in EMBO Reports.

Huntington's disease is a fatal genetic condition currently affecting over 30,000 people in the USA, with a further 200,000 at risk of development later in life. The disease causes deterioration of physical and mental capabilities of patients over several years and is incurable.

Researchers began to investigate the effects of Huntington's on cancer after finding that Huntington's patients have significantly lower rates of cancer development than the general population, with 80 percent fewer cases.

Huntington's disease is caused by the over-abundance of a repeating sequence 'CAG' in the DNA of a protein called huntingtin. When transcribed, this repeating sequence forms several small interfering RNA molecules (siRNAs) which attack other genes essential for cell survival. The more CAG repeats present in a patient's gene, the faster they will develop the associated disease.

While previously observed that nerve cells are susceptible to cell death via the activity of huntingtin, the researchers have now identified that cancer cells are also highly susceptible to destruction by siRNA.

In order to test the hypothesis in a treatment scenario, Dr Peter worked alongside Dr Shad Thaxton, also at Feinberg to use nanoparticles to deliver huntingtin to mice with human ovarian cancer. The treatment significantly reduced tumour growth with no associated toxicity in the mice.

Their colleague Dr Andrea Murmann, also at Feinberg, used huntingtin to treat a range of cancers found in humans and mice, including brain, lung, skin and breast cancers. The protein was toxic to all tested cancers in both species.

'We believe a short-term treatment cancer therapy for a few weeks might be possible, where we could treat a patient to kill the cancer cells without causing the neurological issues that Huntington's patients suffer from,' said Dr Peter.

The group is now working to refine the delivery mechanism,  aiming to improve the efficacy of this molecule reaching tumour sites. They are also working on stabilising and creating effective storage methods for the nanoparticles involved in protein delivery.

Huntington's disease provides new cancer weapon
Northwestern University |  12 February 2018
Huntington’s ‘super assassin’ gene offers hope for cancer treatment
i news |  12 February 2018
Huntington's 'super assassin' molecule could kill cancer
Medical News Today |  13 February 2018
Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells
EMBO Reports |  12 February 2018
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