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2nd October 2017

New anti-inflammatory compound developed by Manchester researchers

Researchers at the University of Manchester have developed a new anti-inflammatory compound which may hold promise for conditions such as Alzheimer’s disease
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Inflammation is a normal and healthy part of our immune systems and forms part of your body’s innate response to infection. Unfortunately, despite our bodies being adept at dealing with a range of challenges, they can make mistakes. In the case of inflammation, this can lead to the destruction of healthy cells and lead to inflammatory illnesses such as Crohn’s disease and arthritis.

In the case of inflammation, this can lead to the destruction of healthy cells and lead to inflammatory illnesses such as Crohn’s disease and arthritis.

There is a broad range of illnesses which have been shown to have an immune component to them: Alzheimer’s disease, schizophrenia, depression, atherosclerosis and diabetes, to name a few. However, there are currently few effective treatments available and most only manage the symptoms with varying levels of success.

This is where a group of researchers at the University of Manchester comes in. A team led by biologist Dr David Brough and chemist Dr Sally Freeman have recently developed a new molecule capable of reducing inflammation by targeting a component of the immune system known as the inflammasome.

The inflammasome is a complex structure which coordinates inflammation by mobilising chemical foot-soldiers known as cytokines.

There are many different types of inflammasomes but one commonly associated with disease, and targeted by the researchers in this study, is referred to as NLPR3. For example, this inflammasome NLPR3 has been associated with Alzheimer’s disease for which treatment mainly involves management of symptoms as they occur.

The ability to target, and switch off, the NLPR3 inflammasome would open up new treatment targets for Alzheimer’s disease and other chronic illnesses associated with faulty inflammation.

In an open-access article published in Cell Chemical Biology, the Manchester-based team created their new anti-inflammatory molecule from a basic compound (2-APB) which targeted the inflammasome but also other important cell functions. This made it not particularly useful in treating disease as the other functions it targeted are vital to the healthy functioning of cells.

Therefore, the researchers slowly but steadily altered the structure of this compound, tested it, altered it some more, tested it, and over many iterations they finally produced a molecule which specifically targeted the inflammasome.

This final molecule (‘Novel Boron Compound 6’ or NBC6) was also found to inhibit inflammasome NLPR3 better than the original non-specific compound (2-APB). The researchers tested NBC6 on mice and found promising results.

This research supports a previous article published in Nature Communications by the same group last year which showed that targeting the NLPR3 inflammasome could reduce Alzheimer’s symptoms in a mouse model of the disease.

The development of this new anti-inflammatory molecule, NBC6, opens-up another avenue for research into treatments for inflammation-mediated illnesses by targeting the NLPR3 inflammasome.

One of the researchers involved on the project, PhD student Mike Daniels has this to say about the research: “This is a really exciting study and it feels fantastic to finally get this out there. We are in desperate need for new treatments for diseases such as Alzheimer’s and, although NBC6 won’t be an effective drug, it’s certainly a step along the way.”

It is important to note that this is a starting point in the development of drugs from this molecule. There are many more hurdles which this molecule will have to advance through before we start seeing its use in humans who suffer from inflammatory illnesses.

Nonetheless, it is an exciting advancement and one of many steps to help rectify faults in the natural and protective process of inflammation.

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