Huntington's Disease Gene Deadly to Cancer Cells

Patients with Huntington’s disease, a rare genetic condition, have been found to be 80% less likely to develop cancer compared with the general population. The underlying cause of the dramatic disparity in cancer occurrence among patients with this orphan disease was largely a mystery.

A study published by EMBO Reports has uncovered why Huntington’s disease is so harmful to cancer cells. The authors of the study have also developed a novel way to fight cancer based on these findings.

Huntington’s disease is caused by repeating RNA sequences in the huntingtin gene in every cell. The repeating sequences of small interfering RNAs attack genes vital for survival. The defect is toxic to both brain and cancer cells, according to the authors.

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"This molecule is a super assassin against all tumor cells," said senior author Marcus Peter, PhD. "We've never seen anything this powerful."

To determine the efficacy of the molecule as a treatment, the researchers loaded it into nanoparticles that were then administered to mice models of ovarian cancer.

The authors discovered that this treatment reduced cancer growth with no toxicity or adverse events. Notably, mice models did not develop resistance to the nanoparticle-based therapy, according to the study.

The researchers are currently working to optimize this delivery approach and improve its ability to reach the tumor. Determining how to stabilize the nanoparticles to allow for storage is also an important part of developing this strategy into a drug, according to the study.

In a further analysis, the molecule was used to treat ovarian, breast, prostate, liver, brain, lung, skin, and colon cancers in human and mice cell lines. The therapy was observed to neutralize all cancer cells in both humans and mice, according to the study.

These new findings build on previous research that uncovered a “kill switch” in all cells that targets 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,” said first and co-corresponding author Andrea Murmann, PhD. “These patients would not only have a disease with an RNA component, but they also had to have less cancer.”

When looking specifically at the repeating sequences in huntingtin, the researchers noticed a similar composition to the kill switch, which were both were rich in the C and G nucleotides, according to the study.

“Toxicity goes together with C and G richness,” Dr Murmann said. “Those similarities triggered our curiosity.”

These results may lead to more optimal cancer treatment with limited toxicity; however, human clinical trials are necessary to confirm the effect.

“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,” Dr Peter said.