Novel discovery benefits chemo patients

By | Health & Wellness
Monocytes, a type of white blood cell shown above, have been shown to infiltrate the nerve cells to help reduce inflammation caused by chemotherapy drugs. However, they also release compounds that activate the receptors in these nerves, sending signals interpreted as pain by the brain. Scientists hope to target these monocytes to develop better relief for chemotherapy patients. Credit image@ BruceBlause, wikimedia commons

The treatment of cancer with chemotherapy uses varying drugs, depending of the type of condition the patient is diagnosed with. Some of these drugs have several side effects, including nerve deterioration, which translates as pain in certain patients.

However, novel research conducted by specialists from the UK’s very own Kings College London, has uncovered new targets, reports a study funded by the Biotechnology and Biological Sciences Research Council.

These new targets mean that scientist can develop compounds in order to provide better and more efficient relief for patients. Drugs like Oncovin, Vincasar, Fludara and Oforta, whilst developed to treat cancer, have side effects on the nervous system, causing detriment to the nerves resulting in discomfort, with over seventy per cent of users developing such secondary affects.

As a result, physicians typically prescribe medication to counter these secondary effects, drastically improving the patient’s quality of life. However, occasionally these affects persist, despite the additional medication prescribed to deal with these neural symptoms. The symptoms often occur in the peripheral nervous symptoms, like the fingers and hands, and range from tingling sensations to more prominent symptoms.

In order to better understand the phenomenon, the Kings College team looked into the mechanisms behind the generation of the symptom as a result of chemotherapy drugs. By investigating why certain drugs often caused these side effects, the team hoped to solve the condition, thus providing relief to its users.

Laboratory mice were used in the investigation, as they also show the symptoms when given chemotherapy medication, like soreness in the hind limbs. They were given doses of the compound vincristine sulfate (VCR), which is also used in humans.

Observations of the laboratory rodents showed the precise mechanism that was generating the side effects: the patients very own immune cells. The chemotherapy medication acted on the blood vessels surrounding the nerves, causing inflammation. The latter draws the attention of the immune system’s white blood cells, acting as a beacon, drawing them towards the site. Here, the researchers found immune cells known as CX3CR1+ monocytes

Normally, white blood cells are found in the blood and lymphatic system, only leaving these areas when dealing with a pathogen or inflamed tissue. Thus, in order to access the vascular tissue around the nerves in an attempt to reduce the inflammation, the white blood cells exited the blood flow and entered the nervous system, squeezing in between adjacent nerve cells.

Once there, the white blood cells release chemicals in order to abate the affected tissue, as well as compounds known as reactive oxygen species. These also cause the nerve cells to activate TRPA1 receptor in sensory nerves, resulting in signals being sent to the brain.

This type of pain is known as allodynia, a term used to describe stimuli which usually bears little responsibility for provoking a pain response. Interestingly, mice who were void of the CX3CR1 antigen on their immune cell surface, only felt the allodynia much later than there other rodent counterparts.

Thus, by developing drugs that reduce the incidence of these white blood cells exiting the blood stream, such as CX3CR1 antagonists for example, would positively affect patients on chemotherapy medication.

Speaking during the news release on the Biotechnology and Biological Sciences Research Council website, Dr Marzia Malcangio, co-author of the paper said the team discovered that the patient’s responses to chemotherapy “are caused by local activation of pain nerves by immune cells and that this could be prevented. Our result can be exploited to produce drugs that, given in combination with treatment, may limit the pain experienced by patients during chemotherapy cycles”.

What other sectors of medical science could this research be applicable to?


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