Tailored treatments closer for immune diseases, says ANU award winner

Personalised and tailored treatments for autoimmune diseases may be only a matters of years away, according to the ANU’s Professor Carola Vinuesa, whose pioneering work has been honoured with two awards from the National Health and Medical Research Council.

Professor Vinuesa, from The John Curtin School of Medical Research (JCSMR), was part of a team, that also included Dr Anselm Enders and Dr Simon Jiang, named as the NHRMC’s top Project Grant application.

She was also named as the NHMRC’s top female researcher in biomedical science in 2016, winning a prized Elizabeth Blackburn Fellowship for a second time.

The awards were announced at the recent annual NHMRC research excellence awards.

Head of the Department of Immunology and Infectious Disease at JCSMR and Joint Director of the Centre for Personalised Immunology (CPI), Professor Vinuesa has helped pioneer research into personalised medicine, using genetic sequences to tailor treatments for patients with systemic lupus and related autoimmune diseases.

Professor Vinuesa said her team had started clinical trials in mice and it should not be too many years before they will have effective drugs for at least some of the genetic pathways the researchers are identifying.

One of the awards honours new research with colleague Ilenia Papajust just published in Nature that has identified a pathway unique to humans that offers another target for boosting or modulating the immune system to treat disease.

“We found the type of neurotransmitters that we thought normally were only functioning in the brain – dopamine, a type of hormone that controls motivation and happiness – also acts in the immune system.

“It’s transmitted across synapses between two cell types that control the production of antibodies – T cells and B cells – and we found that it works in a very intriguing and beautiful mechanism that enhances the interaction and the help B cells get from T cells so that we produce a faster and bigger response to infection.”

She said it was surprising because the immune system in mice and humans was thought to be over 90 per cent identical and most of the team’s models to investigate the immune system have mostly been mice.

“We know what the important receptor for dopamine in this immune response is and it gives us yet another target for not only boosting the immune system when we want to get more effective vaccines, but also dampening the immune system with blockades of this dopamine receptor when we want to, for example, treat autoimmune diseases or a system that is overreactive.”

Professor Vinuesa said new drugs may need to be discovered but there are already many available. The problem is knowing which patients will respond to which drugs.

“Knowing what mutations each patient has allows us to predict which is the best drug for the patient,” she said.

“In some cases we don’t have drugs yet so yes there will be need to be more drug discovery, but in others we have the drugs and instead of having to treat the patients blindly with one drug after another one until something works we will much more rapidly start with the drug which will be effective.”

She said new technologies had been developed to reproduce the same mutation found in patients in mice.

“We can use this mouse model first to test the drug we have available so it makes the research much more meaningful, we don’t need to use models that are not very relevant for human species, we are using the precise mutation we find in patients,” Professor Vinuesa said.

However, the problem is complex because patients have more than just one mutation which increases the difficulty of finding a single drug.

“But it does point to particular pathways, particular areas or branches of the immune system so it helps us get closer to the mechanism of disease,” she said.

She believed this was the way forward in treating disease because “until we understand the mechanism of disease we will not be able to have effective therapies, so by understanding the genetic causation, the molecular mechanism, we get closer to finding treatments that will be more effective and targeted.”

But it’s not all genetics. Environmental causes such as viral infection, diet, and environmental insults such as UV exposure, also have to be taken into account.

Professor Vinuesa said her approach was accepted elsewhere but what’s unique about the Canberra research was the way it closed the loop.

“So not only do we start from the patients and identify the mutations but we also go that extra step to generate the mouse models carrying the mutations so that we can then understand disease and use mouse models to look for effective therapies,” she said.

It was a team effort and required many disciplines. She also acknowledged the support of ACT Health, saying the Canberra Clinic of Genomics, led by the co-director of the CPI, Professor Matthew Cook, was now a template for genomic diagnosis in Canberra.

“We are very proud of now having now a pipeline that’s starting to be a good template for immunology and for personalised medicine in general,” she said.

“It’s an exciting time for all of us. The potential is there, we are going to see a few very exciting years ahead.”