Imagine waking up one day with a devastating condition that has no cause, no test, no treatment and no cure. That’s the reality for up to 250,000 色情网站ns who have myalgic encephalomyelitis (ME), also called Chronic Fatigue Syndrome (CFS). They live with devastating symptoms – crippling fatigue, memory problems, pain and balance issues. And medical science has been powerless to help them.
Professor Sonya Marshall-Gradisnik, Director of the National Centre for Neuroimmunology and Emerging Diseases, is determined to change that. She’s been fascinated by the immune system since her schooldays. “I did advanced science all the way through high school,” she says. “Science was inquisitive. It was curious. It satisfied my thirst for wanting to know new things. And immunology governs nearly everything in our bodies. It’s so complex in its interface with other systems in the body.”
Finding threats
Her work on ME/CFS looks at on what’s known as ‘natural killer’ cells – one of our immune system’s cleverest weapons. While normal immune cells focus on destroying threats that are easy to identify – such as bacterial infections – natural killer cells have a much harder job. They look for the threats which come in disguise.
These threats look like ordinary healthy cells, but they’ve been hijacked by a virus or compromised by cancer. They’re much harder for our immune system to spot and neutralise. However, natural killer cells can find them. Think of them as the Sherlock Holmes of the immune system. And Marshall-Gradisnik reckons natural killer cells might have a part to play in solving the mystery of ME/CFS.
Building the case
Early in her career, she learned about research which revealed that the natural killer cells of people with ME/CFS don’t function properly. But this insight came from studies that just took a single snapshot of a patient’s immune system. Marshall-Gradisnik wanted to see if the problem was ongoing. So she and her colleagues enrolled 65 patients with ME/CFS, along with 21 non-fatigued controls, and studied their natural killer cell activity for a year.
The result? They found that natural killer cells from those with ME/CFS are indeed much less effective. So if you have ME, your natural killer cells are more Dr Watson than Sherlock Holmes. They aren’t so good at finding and destroying deadly cells.
Now the team had to work out why the natural killer cells weren’t working properly. Their theory was that a type of receptor called a threat receptor might be involved. It’s found on the surface of most cells and is responsible for bringing calcium – which is essential for cell function – into the cell.
Inventing experiments
To prove it, they had to precisely measure the changes in these receptors and the calcium channels they guarded. There was just one problem: no technique existed for doing that. So Marshall-Gradisnik developed this natural killer cell receptor technique.
“We spent 18 months developing it,” she says. “I think it’s the hardest thing I’ve ever had to do in my career.” It involved placing the tips of microscopic glass pipettes onto either side of the receptor – which is itself just millionths of a metre in size – to measure if this receptor was faulty and if the movement of calcium was impacted, but without damaging the fragile receptor in the process.
The results were worth the effort. Just as the team thought, the receptor on the natural killer cells wasn’t functioning as it should. It was adversely impacting on calcium, meaning the cells couldn’t do their job properly.
Improving lives
Armed with this knowledge, Marshall-Gradisnik and her team are now determined to crack even bigger challenges: creating a diagnostic test and an effective treatment. The team is just about to begin a clinical trial of Naltrexone – more commonly known as a treatment for opioid or alcohol addiction disorder – which seems to make this receptor work better, according to existing research.
“During the COVID-19 pandemic, we recruited four people that had ME and were taking low dose Naltrexone,” she says. “The hypothesis was that they would have restored receptor function and natural killer cell function – and they did. That gave us the evidence to apply for a grant and run a clinical trial.” Marshall-Gradisnik and her team have also shown that long COVID patients have the same faulty receptors as those with ME; they will shortly be embarking on a trial with those patients, too.
It’s a huge challenge – and a long road. But their research is already improving lives. “Patients just want to feel better,” she says. “Our mission is that patients are our first priority. The research we’ve done has changed clinical guidelines. Our research has informed that change. That’s what researchers set out to do. We make a positive impact by improving people’s lives.”
Our researchers are making a real difference to people’s lives. Find out more about the and discover how your nose cells could help people walk again.
Image captions (top to bottom)
- Standing up and making it count for ME/CFS and Long COVID patients.'
- Dream Team making a difference.
- A happy team kicking goals for patients.
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