{"id":624,"date":"2019-01-09T12:42:19","date_gmt":"2019-01-09T12:42:19","guid":{"rendered":"http:\/\/horizon.peachpuff-wolverine-566518.hostingersite.com\/?p=624"},"modified":"2019-01-09T12:42:19","modified_gmt":"2019-01-09T12:42:19","slug":"understanding-immune-system-switches-will-spark-new-drugs","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/horizon\/624\/understanding-immune-system-switches-will-spark-new-drugs\/","title":{"rendered":"Understanding immune system switches will spark new drugs"},"content":{"rendered":"

Identifying the chemical switches that turn different parts of our immune system on and off is opening up new avenues for treating diseases such as Parkinson\u2019s, Alzheimer\u2019s, cancer and rheumatoid arthritis \u2013 and potential new uses for discarded drugs, according to Professor Luke O\u2019Neill, an immunologist at Trinity College Dublin, Ireland.<\/strong><\/h3>\n
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Your work focuses on the innate immune system. Can you explain what this is?<\/strong><\/p>\n

\u2018In the past, scientists paid most attention to the adaptive immune system, which is the part that has antibodies that memorises invaders. Most of life on Earth does not have antibodies and defends itself with what we call the innate immune system. I\u2019ve been figuring out the component parts, like the way you\u2019d take apart a car engine. We didn\u2019t know what half the parts of the innate immune system even were. Now that we know more, we are creating drugs (that target this process) to help patients.\u2019<\/p>\n

One of the effects of the innate immune system is inflammation. Why is this an important area of research?<\/strong><\/p>\n

\u2018The normal job of inflammation is to fix tissues. If you sprain your ankle and get an injury, inflammation is triggered to repair the wound.<\/p>\n

\u2018What\u2019s amazing is that inflammation lies at the heart of so many diseases, when it gets out of control. That could be Alzheimer\u2019s in the brain, rheumatoid arthritis in joints, Crohn\u2019s disease in the gut or arteriosclerosis in the blood vessels. Steroids work for several of these diseases. Though steroids have side effects, this shows the diseases follow a common pathway. This gives us hope that if we can find specific pathways we could treat patients with different inflammatory disorders.\u2019<\/p>\n

Can you give us an example of where this approach is showing promise?<\/strong><\/p>\n

\u2018A type of protein called Toll was discovered in fruit flies, and then versions were found throughout nature. We realised they were important more generally in the innate immune system of organisms, including in people. My lab looked at how (toll) receptors triggered macrophages (immune cells that attack bacteria and other invaders), and discovered a key switch called MAL. These discoveries provided new targets to fire drugs at.<\/p>\n

\u2018My interest is mainly in inflammatory diseases like rheumatoid arthritis. The macrophages in rheumatoid arthritis patients somehow get reprogrammed to be overactive, for months on end. Blocking certain toll-like receptors could turn down inflammation and treat patients.’<\/p>\n

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‘What\u2019s amazing is that inflammation lies at the heart of so many diseases, when it gets out of control.’<\/p>\n

Luke O\u2019Neill, Trinity College Dublin, Ireland<\/p>\n<\/blockquote>\n<\/div>\n

What other examples of chemical switches there?<\/strong><\/p>\n

\u2018What\u2019s really exciting right now are checkpoint proteins, which were discovered a number of years ago. These are off-switches in the immune system to stop it running out of control. One is called PD1. A (cancer) tumour flicks the off switch, a cunning strategy to stop itself from being attacked. Now drug companies have developed a way to block that off-switch using checkpoint blockers. Once you do that, the cancer can be attacked by the immune system. We\u2019ve been studying these switches.\u2019<\/p>\n

What\u2019s next?<\/strong><\/p>\n

\u2018The brain has come into focus. We are more aware now that immune dysfunction is involved in diseases like Alzheimer\u2019s and Parkinson\u2019s disease, but also depression and, amazingly, schizophrenia too.<\/p>\n

\u2018(We are) looking to block inflammasomes. These are switches on macrophages, which are frontline immune cells, that sense danger. If they detect something noxious, such as the beta-amyloid proteins in Alzheimer\u2019s, they drive inflammation. We could stop inflammation going into overdrive and perhaps get new medicines for Parkinson\u2019s and Alzheimer\u2019s. Wouldn\u2019t that be great?\u2019<\/p>\n

Recently you happened upon a drug that had been tested and dropped, but you believe this drug can be used for patients?<\/strong><\/p>\n

\u2018Pfizer had discovered a compound, but dropped it for various reasons. We found that it blocks the NLRP3 inflammasome. The compound worked in models of multiple sclerosis, in sepsis, in Parkinson\u2019s disease and in Alzheimer\u2019s too. We were keen to take this further and we set up a company (in 2016) to do so, Inflazome.<\/p>\n

\u2018There are lots of compounds on the shelf that drug companies could take down and dust off. Often they see side-effects and that puts them off, especially if they do not know how the compounds works.\u2019<\/p>\n

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\"Immunologist
Immunologist Prof. Luke O\u2019Neill says inflammation lies at the heart of many diseases. Image credit – Trinity College Dublin<\/figcaption><\/figure>\n<\/div>\n

You also worked on the MICROINNATE project which looked at RNA switches. Can you tell us about that?<\/strong><\/p>\n

\u2018MicroRNAs were discovered about 15 years ago. These are small pieces of RNA that can stop cells making specific proteins. My lab was one of the first to discover their role in the innate immune response and we found that they were one of the key controllers in immunity. Efforts to use them as a therapeutic stalled initially, but there are now companies looking to use RNA as a drug.\u2019<\/p>\n

You are a busy researcher, but you\u2019ve taken time to set up companies: why?<\/strong><\/p>\n

\u2018As a scientist, your main passion is to make discoveries. If you do find something interesting, what do you do next? It\u2019s taxpayers\u2019 money funding research, so you have an obligation to exploit these discoveries or to pass it on to someone who will. One way is to form your own company. The biggest thrill is to help patients. That is always at the back of your mind. Imagine if your discovery, from noodling as I call it, makes a difference to people\u2019s lives.\u2019<\/p>\n

The MICROINNATE project was funded by the EU\u2019s European Research Council. If you liked this article, please share it on social media.<\/em><\/p>\n

Originally published on Horizon<\/a><\/em><\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Identifying the chemical switches that turn different parts of our immune system on and off is opening up new avenues for treating diseases such as Parkinson\u2019s, Alzheimer\u2019s, cancer and rheumatoid arthritis \u2013 and potential new uses for discarded drugs, according to Professor Luke O\u2019Neill, an immunologist at Trinity College Dublin, Ireland. Your work focuses on … Read more<\/a><\/p>\n","protected":false},"author":320,"featured_media":625,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"generate_page_header":"","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[12],"tags":[37,25,95,79,24],"class_list":["post-624","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","tag-health","tag-innovation","tag-medicine","tag-research","tag-science"],"yoast_head":"\nUnderstanding immune system switches will spark new drugs - Horizon Magazine Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/horizon\/624\/understanding-immune-system-switches-will-spark-new-drugs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Understanding immune system switches will spark new drugs\" \/>\n<meta property=\"og:description\" content=\"Identifying the chemical switches that turn different parts of our immune system on and off is opening up new avenues for treating diseases such as Parkinson\u2019s, Alzheimer\u2019s, cancer and rheumatoid arthritis \u2013 and potential new uses for discarded drugs, according to Professor Luke O\u2019Neill, an immunologist at Trinity College Dublin, Ireland. 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And among the different candidates is a new player on the scene \u2013 mRNA vaccines. One mRNA\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"According to Prof. Bekeredjian-Ding, an approved mRNA coronavirus vaccine would be easier and faster to produce and thus deploy worldwide than a conventional vaccine. 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We often think about vaccines protecting us against a\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/11\/kid-vaccine-sm.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/11\/kid-vaccine-sm.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/11\/kid-vaccine-sm.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/11\/kid-vaccine-sm.jpg?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2020\/11\/kid-vaccine-sm.jpg?resize=1050%2C600&ssl=1 3x"},"classes":[]},{"id":1449,"url":"https:\/\/scienceblog.com\/horizon\/1449\/qa-cancer-vaccines-will-not-replace-surgery-or-chemo-but-could-give-long-lasting-immunity\/","url_meta":{"origin":624,"position":3},"title":"Q&A: \u2018Cancer vaccines will not replace surgery or chemo but could give long-lasting immunity\u2019","author":"Horizon Magazine","date":"September 24, 2020","format":false,"excerpt":"by\u00a0Ian Le Guillou A cancer vaccine needs to tackle the dual issues of cancers being able to hide from the immune system and suppress our immune defences. Recent advances are bringing cancer vaccines much closer to reality, giving patients another weapon in their arsenal of cancer treatments, according to Dr\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"A cancer vaccine needs to tackle the dual issues of cancers being able to hide from the immune system and suppress our immune defences. 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Immunotherapy drugs are specifically designed to help the immune system respond to cancerous cells, something that it doesn\u2019t naturally\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"Researchers in the Netherlands are hoping to move vaccine therapy from the lab to inside the body.","src":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2018\/02\/petri-dish-2000-e1648216038606.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2018\/02\/petri-dish-2000-e1648216038606.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2018\/02\/petri-dish-2000-e1648216038606.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2018\/02\/petri-dish-2000-e1648216038606.jpg?resize=700%2C400&ssl=1 2x"},"classes":[]},{"id":1282,"url":"https:\/\/scienceblog.com\/horizon\/1282\/the-aim-is-to-find-the-monoclonal-the-hunt-for-the-antibody-to-treat-covid-19\/","url_meta":{"origin":624,"position":5},"title":"\u2018The aim is to find the monoclonal\u2019: the hunt for the antibody to treat Covid-19","author":"Horizon Magazine","date":"May 14, 2020","format":false,"excerpt":"by\u00a0Ian Le Guillou Transfusing antibodies from Covid-19 survivors into seriously ill patients could provide a quick treatment win, but a more selective approach may both treat and prevent the disease. A single, highly-effective antibody that is mass-produced like a drug could combine the benefits of antivirals and a vaccine for\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"If researchers could find the most effective antibody against coronavirus, it could act as both a cure and temporary vaccine. 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