Huntington’s disease causes critical degradation of a patient’s nervous system.

Researchers at Northwestern University Feinberg School of Medicine believe they have identified the mechanism by which Huntington’s disease (HD) represses cancer proliferation in patients. The study, which was published yesterday in EMBO Reports, could provide researchers with a new avenue through which they can treat cancer.

Huntington’s disease is an inherited, genetic condition that causes an overabundance of repeating RNA sequences in the huntingtin gene. Over time, this mutation causes degradation of the patient’s nervous system, leading to uncontrollable movements, emotional imbalances, and reduced cognition. The disease is usually fatal within twenty years of diagnosis and there are currently no treatment options available. One feature of HD that has vexed researchers is that patients with the Huntington’s gene demonstrate a much lower rate of cancer in comparison to the general population, with an average of 80% fewer cases.

To investigate this phenomenon, a team of researchers at Northwestern began to investigate the link between the two diseases. Through their research, they identified a small interfering RNA (siRNA) produced by a mutated huntingtin gene that causes brain cell death in Huntington’s. Further research into the molecule revealed that it is also a highly effective tool for eradicating cancer cells.

“This molecule is a super-assassin against all tumour cells,” said Marcus Peter, PhD, Professor of Cancer Metabolism at Northwestern and senior researcher for the study. “We’ve never seen anything this powerful.”

The siRNA’s effectiveness against cancer cells makes it a very interesting prospect for cancer treatment. To investigate the molecule’s potential, the Northwestern team encapsulated it in nanoparticles and delivered it to mice with human ovarian cancer. They found that the siRNA significantly reduced tumour growth and, importantly, the team did not identify any toxicity to healthy cells or development of drug resistance within the cancer cells.

With their early results promising, the team moved on to testing the siRNA against human and mouse forms of ovarian, breast, liver, brain, skin, prostate, lung, and colon cancers. In all cases, the siRNA was able to effectively kill the cancer cells.

“While the treatment with siCAG/CUG requires optimization, our data on the toxicity of CAG Trinucleotide Repeat-based siRNAs for cancer cells but not normal cells when administered in vivo and the reported decreased incidence rate for different types of cancer in patients with CAG expansions suggest that TNR-based siRNAs may be useful for cancer therapy,” the authors concluded.

The team now hope to test the siRNA on a range of cancers in clinical trials, with the intention of producing a short-term cancer therapy. They believe that if the treatment is limited to short doses, patients will not experience the neurological deterioration that is characteristic of Huntington’s.