Molecule behind Huntington’s disease found to be cancer-killing “super assassin”.

For several years, scientists have noticed an unexplained reduced incidence of cancer in patients suffering from the devastating hereditary neuro-degenerative condition Huntington’s disease. Now a team at Northwestern Medicine has uncovered how the disease could be inadvertently killing cancer cells, and how this process could be harnessed for a new cancer treatment.

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The same molecule that causes Huntington’s disease has been found to have remarkable cancer-killing properties

Huntington’s disease is caused by a mutation in a gene called huntingtin. The mutation generates repeating RNA sequences and these repeating sequences, known as small interfering RNAs (siRNAs) are what slowly damage neural cells, causing the progressive neuro-degeneration associated with the condition.

Previous research by the same Northwestern team discovered that siRNA molecules were amazing cancer-killing assassins that evolved in living organisms millions of years ago to fight cancer before the more complex adaptive immune system developed. This research inspired the team to investigate whether there were diseases involving similar RNA mechanisms that also correspond with lower rates of cancer.

“I thought maybe there is a situation where this kill switch is overactive in certain people, and where it could cause loss of tissues,” says first author on the study Andrea Murmann. “These patients would not only have a disease with an RNA component, but they also had to have less cancer.”

The repeating siRNA sequences found in Huntington’s pathology were discovered to be very similar to the siRNA molecules identified in the team’s earlier work. So the next step was to test whether this particular molecule, when delivered via nanoparticles to mice, actually worked to kill cancer cells. The results were remarkable. Tumor growth was significantly reduced in a huge variety of different cancer cell lines, including ovarian, breast, prostate, liver, brain, lung, skin and colon cancer cells.

“This molecule is a super assassin against all tumor cells,” say senior author Marcus Peter. “We’ve never seen anything this powerful.”

The next step for the researchers is to work on refining the nanoparticle delivery method so that the cancer-killing molecules can be more accurately delivered to a target tumor. This is obviously several years away from becoming an approved clinical treatment, and it is still unknown whether administering these damaging molecules to neurologically healthy humans would cause Huntington’s-like symptoms.

The researchers suggest that Huntington’s patients are exposed to these toxic RNA sequences for decades before the damage is great enough to cause clinically-observable symptoms, so this may lead to a viable short-term cancer treatment.

“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,” says Marcus Peter.

The research was published in the journal EMBO Reports.

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