Finally Australian researchers develop world first method of treating lupus

Two years away from clinical trials, the method targets the T-cell in the immune system – offering patients the possibility of a treatment beyond medication and its side effects.

For Vu Nguyen, having the chronic inflammatory condition lupus has been debilitating.

Diagnosed at the age of nine, she has lived with it now for 30 years – and it has had huge impact on her life.

It was 1995 – so back then it wasn’t very well-known. The first symptoms I had were aching joints, swollen joints. So I went to the GP. Luckily, he was reading up on it and he said maybe go do these blood tests. And it turned out I had lupus. When I was about 22, I actually had a stroke, which is caused by the lupus. So about a year after being in hospital, I was diagnosed with epilepsy as well. So after that I was told you can’t really work because stress will activate the epilepsy and (lead to) seizures).”

Like other autoimmune diseases, there is no cure.

To manage the symptoms, patients use lifestyle interventions and take regular medications with potential toxic side effects.

The condition is estimated to affect 1 per cent of Australians – that’s 25,000 people – with higher prevalence among women in their childbearing years – and those who are Indigenous Australian, Polynesian or of South East Asian descent.

It presents differently in individuals, producing antibodies in the immune system that attack multiple organs in the body: from skin and joints – to the kidneys, heart and brain.

For women in their 20s and thirties, it confers a 1 in 10 chance of dying before the age of 40 [[according to a 2012 meta-analysis of global data published in the journal, Seminars in Arthritis and Rheumatism]].

For Ms Nguyen, her lived experience with the disease led her to establish patient support group, Lupus Victoria, to help people navigate the ups and downs.

“With lupus it’s very unusual to have some symptoms. So sometimes, people come on and ask: is this unusual? What can I use for my itchiness – things like that. People (in the group) will give their input. You should think about this, read this book, exercise. You should try this ointment. I think with the group – because lupus is unknown now; sometimes families of newly diagnosed patients still don’t understand. So at least they’re coming there and they’re able to talk to people to know what’s going on. And it really helps them that way.”

Now, researchers at Monash University have progressed a six-year project that could lead to the development of the first long-term treatment option for lupus patients.

The research is two years away from clinical trials.

Project lead Associate Professor Joshua Ooi says the team of 22 researchers were able to target a specific human cell in lupus patients – and reprogram it using protective molecules from healthy people.

“These patients have T-cells that target themselves; and we engineer these regulatory T cells that stop these T cells from doing that. Patients with these autoimmune diseases, they’re lacking this particular gene or the receptor. So what we do is we take these cells out, reset them, put the right receptor on them; and then basically fix the immune system. So we give the immune system a reset – like a software upgrade to get everything working properly again.”

The team were able to use the resource of the Australian Lupus Registry and Biobank – established at Monash University in 2012 – to test the idea.

The method was developed using patient cells in test tubes – and then tested in pre-clinical models using mice.

Associate Professor Ooi says the next stage is to see how it performs in a clinical trial of between 10 and 20 Australian patients.

“Proof will happen when we actually do the clinical trial. I mean, as a scientist myself for nearly 20 years, I think we get very excited about things that happen in the test tube or in models of disease. But proving it in an actual patient would be the key bit of results that will convince me and everybody else that it actually works.”

He says the specific and targeted nature of the intervention has minimised the side-effects – and it will be something closely watched in the clinical trial.

“They have to take regular medication, whereas these cells that we put in the body, they actually live in the body for at least a few years. So we hope it’s going to be a much better, safer, easier treatment to take. We are only modifying the genes in a very small subset of cells. It’s not changing your whole genome. You can’t pass it on to your children, and once these cells do what they’re supposed to do in the body, there’s nothing to suggest that it would cause anything harmful. Plus, the cells that we are engineering, they are anti-inflammatory, so they’re unlikely to cause any sort of bad side effects.”

The work has been published in peer-reviewed journal Nature Communications.

Study co-author Peter Eggenhuizen says there is real potential for the method to be adapted to treat up to 100 other autoimmune diseases, including diabetes, rheumatoid arthritis and multiple sclerosis.

“This new pipeline that we’ve uncovered to find these protective molecules can then be used to target each disease to find a receptor against each disease and put it on your cells to restore that balance in the immune system that is lacking in these patients. We’re currently in development in earlier stages for other autoimmune diseases, looking for protective molecules to target these diseases such as type 1 diabetes and also inflammatory bowel disease.”

Professor Fabienne Mackay at the Q-I-M-R Berghofer Medical Research Institute was not involved in the study.

She says the clinical trial results will need to further validate the approach, but the testing of specific patient cells in the study is significant – and a much better solution than the impact of current treatments that destroy both bad and good cells in the immune system.

“I think it’s very exciting. It’s actually a very good study and I’ll tell you why, because you have to go back to what the treatments are like currently for the treatments of lupus. And those treatments always call them very blunt instruments. They are meant to suppress inflammation, but they do it in a very undiscriminating way in really immunocompromised patients. They just shut down the immune system and we’ve seen with Covid that it’s very important to have an immune system working on the side. What this study is doing is something really interesting. It’s actually trying to be a bit more surgical in the way we suppress the dangerous in immune cells that are driving the disease.”

For Ms Nguyen, she says it is encouraging to see progress towards a potential long-term treatment that could substantially improve quality of life.

“That (it) could help anyone – because at the moment, so many people are struggling to really live independently. We all need carers around us; and a lot of the people in the group are older generations that are living by themselves – or are with a partner. Whereas people like someone like me, I mean I’m still living at home by myself, but if this could help people like myself get more independent and get out of the house by myself… then hopefully this treatment works.”