Scientists have widely known that cancer can trigger off-the-rails immune responses, which can harm the body's nerve cells. This can lead to cognitive problems and memory loss in cancer patients.
This condition is a type of paraneoplastic neurological syndrome (PNS), and experts are aware that it stems from the reaction of the immune system to a tumor rather than the tumor itself. However, what initially triggers PNS remains a mystery.
Neurological Mechanisms of PNS
The paraneoplastic neurological syndrome refers to rare disorders linked with cancer, although it is not caused by metastasis, direct invasion, or the consequences of treatment. It happens when a tumor sets off an autoimmune response that targets the brain and spinal cord.
In this condition, the immune cells of patients with PNS cause collateral damage to the nervous system. Because of this, the syndrome can occur even if no cancer cells are physically present within the nerve tissue.
Affected patients can sometimes lose memory before the cancer cells are even detected. Sometimes, the cell damage caused by PNS can be worse than the cancer.
PNS can be diagnosed using tests that look for onconeural antibodies in the patient. These antibodies are related to both cancer and neurological symptoms. They can be used to help diagnose the cancer itself. However, scientists are not sure why the body produces these antibodies in the first place.
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Unmasking the Virus-Like Protein
University of Utah Health researchers have reportedly discovered the answer to this mystery. Their findings are discussed in the paper "PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome."
Led by Department of Neurobiology associate professor Jason Shepherd, the research team investigates PNMA2, a gene that encodes a protein exclusively produced in the brain. Antibodies target PNMA in PNS patients with no signs of nervous system degeneration.
After observing the PNMA2 protein with an electron microscope, the scientists realized it looked very similar to a virus. They hypothesized that, due to its appearance, it might have been mistaken by the body's immune system as an invader, producing antibodies against it.
However, PNMA2 is also found in the brains of people who do not have cancer. The researchers hypothesized that if the protein is being made by the cancer cells outside the nervous system, the body might interpret it as being in the wrong place, triggering an immune response.
To test this idea, they injected PNMA2 proteins in the abdomen of mice. The research team found that the animals did not only mount an immune response and make antibodies but also exhibited similar cognitive issues to cancer patients with the same antibodies.
Other proteins form virus-like structures, yet PNMA2 causes such a severe reaction. According to Shepherd, other virus-like proteins are usually transferred out of the cells within enclosed membranes, which lets them evade the immune system.
The study also poses interesting questions, such as whether any virus-like proteins produced in the brain trigger an immune response. In the future, Shepherd and his team plan to study the aspect of the autoimmune response that is most responsible for the neuron damage observed in patients. Answering these questions could someday lead to the development of future treatments.
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