We get numerous itches throughout the day and do not even pay attention to them – a simple scratch with our nails is all it takes to get rid of it. However, for some people scratching does not help and annoying itching stays regardless of efforts to get rid of it. This condition, when itchy sensation never goes away is called “chronic intractable itch”. It is very difficult to treat this condition, but now scientists say they might have found a way.
This condition is closely associated with dialysis and renal failure. There are treatments, but most of them work with inevitable side effects. Now scientists from the Florida campus of The Scripps Research Institute have described a class of compounds, which in the future could be used to make more effective medicine to treat chronic intractable itch. In fact, these compounds are thought to have a potential to stop chronic itch while dodging usual side effects.
Professor Laura Bohn said: “Our lab has been working on compounds that preserve the good properties of opioids and eliminate many of the side effects. The new paper describes how we have refined an aspect of signalling underlying how the drugs work at the receptor so they still suppress itch and do not induce sedation. Developing compounds that activate the receptors in this way may serve as a means to improve their therapeutic potential.”
This compound that is bringing so much promise to the field is called “Isoquinolinone 2.1”. It targets the kappa opioid receptor, which is widely expressed in the central nervous system. The main function of this receptor is to moderate pain perception and stress responses. Scientists thought that by targeting this receptor they could relief the chronic itching sensation and performed experiments to confirm it. As usual, mouse models were used. During the research scientists found that the compound was effective in stopping chronic itching, without causing sedation.
Scientists say that Isoquinolinone 2.1 is just one of the examples of the new class of “biased” kappa agonists, which avoid many central nervous system side effects by preferentially activating a G protein-mediated signalling cascade without involving another system based on β-arrestin protein interactions. In other words, this class of medicine can work extremely effectively, but avoids many side effects that currently used drugs have.
Even if chronic intractable itch seems to be a minor annoyance, rather than a serious condition, scientists have to work on it too. For those who suffer from this condition it is a major discomfort and this new drug candidate may in the future bring relief that would significantly increase life quality. This goes to show that there are no small jobs in science – every little step to better quality of life for people suffering from various conditions and diseases is a step worth taking.