Huntington's disease may become a new weapon against cancer

Release date: 2018-03-14

Huntington's disease is an autosomal dominant neurodegenerative disease, a fatal hereditary disease that causes brain cell death in the brain. Huntington's disease causes the body and mental retardation to occur at the optimal working age. And can't be cured. It usually occurs around 40 to 50 years old, with an average survival of 15 to 20 years after onset. Huntington's disease is generally fatal and there is no effective treatment. However, compared with the general population, Huntington's disease patients can be reduced by up to 80%.

To clarify the relationship between Huntington's disease and cancer, scientists at Northwestern Medicine have discovered why Huntington's disease is highly toxic to cancer cells and use this to find new ways to treat cancer.

The pathogenesis of Huntington's disease

Huntington's disease is caused by the presence of an excess of specific RNA repeats on the gene encoding the huntingtin protein, which is present in all cells. This deficiency, which causes disease, is also highly toxic to tumor cells. These repeats -- in the form of so-called small interfering RNA -- attack certain genes in the cell that are vital to survival. Neurons in the brain are prone to this form of cell death, but cancer cells appear to be more susceptible to infection.

Senior author Marcus Peter said: "This molecule is a super killer of all tumor cells, and we have never seen such a powerful thing." The study was published in the February 12 issue of the European Journal of Molecular Biology.

Nanotechnology boosts treatment methods

To test the therapeutic effects of this super killer, Peter collaborated with Dr. Shad Thaxton, associate professor of urology at Feinberg, to deliver the molecule through nanoparticles to mice with human ovarian cancer. This treatment significantly slows tumor growth and is not toxic to mice. Importantly, the tumor does not develop resistance to this cancer treatment.

Peter and Thaxton are currently optimizing the way molecules are delivered to increase their efficiency in reaching tumors. Another challenge scientists face is finding ways to stabilize the nanoparticles so they can be preserved. The researchers also use this molecule to treat human and mouse ovarian cancer, breast cancer, prostate cancer, liver cancer, brain cell tumors, skin cancer, and colon cancer cell lines. This molecule kills all cancer cells from both species.

"Death switch" caused people to Huntington's disease

Concerned about anticancer effects

Huntington's cancer weapon was discovered by Murmann, who had an early study with Peter and found that all cells that destroy cancer cells have a switch that specifically kills cancer cells. Murmann had previously envisioned that perhaps in some people, this death switch was overactive, causing tissue loss. These patients must not only have diseases involving RNA components, but must also be less susceptible to cancer. Huntington's disease is the most obvious disease that meets these two characteristics.

The study found that the repeats in the Huntingtin gene have similar sequences to the previously discovered death switches, both of which are rich in C and G nucleotides (the basic molecules that make up DNA and RNA). This similarity has caused scientists' curiosity.

In Huntington's disease patients, the Huntingtin gene contains an excess of CAG trinucleotide repeats. The longer the repeat sequence, the sooner the patient becomes ill. Researchers are currently developing short-term cancer therapies for weeks, in which they can treat patients and kill cancer cells without causing the neurological symptoms of Huntington's patients.

Huntington's disease spreads all over the world and affects all ethnic groups. Among them, Caucasians in Europe and America are involved, and the incidence rate is different. There are regional clusters. The research on the pathogenic mechanism of Huntington's disease in China has not been carried out in depth. Activation of the apoptotic pathway is considered to be one of the pathogenesis of Huntington's disease and has become an important and interesting therapeutic target. However, there are few studies between the pathogenesis of Huntington's disease and cancer, and the publication of this study will point the way to the cause of human cancer treatment.

Source: https://medicalxpress.com/news/2018-02-huntington-disease-cancer-weapon.html

Source: CPhI Pharmaceutical Online

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