Dr Marc Ruitenberg’s work on inflammation after SCI

Dr Marc Ruitenberg.

Marc Ruitenberg is an Associate Professor at The University of Queensland and Head of the Laboratory for Central Nervous System Injury and Inflammation Research.

He has a longstanding relationship with SpinalCure Australia that goes back to 2012, when SpinalCure Australia awarded him a prestigious Career Development Fellowship in partnership with The University of Queensland for his work on the inflammatory response to SCI, and the role that this plays in recovery.

SpinalCure continues to provide funding assistance to A/Prof Ruitenberg in recognition of the internationally acclaimed contributions that his group is making to this vital field of research.

Inflammatory response after SCI

“What we are doing in the lab, and also on the clinical side of things, is to really try and understand what happens following a spinal cord injury at the cellular and molecular level, focusing in particular on the inflammatory response,” explained Dr Ruitenberg.

“As with any tissue of the body that gets injured, there are inflammatory changes. With spinal cord injuries, however, these changes do not support wound healing and repair. Rather, what we know is that if they are left unchecked – meaning that if we leave the inflammatory response to develop naturally, without intervention – it will actually cause more damage to the spinal cord then what was inflicted at the time of the accident,” he added.

“This is a very important thing to realise as most injuries are not a complete severance of the spinal cord, and there are thus still very likely connections between above and below the lesion site that we must protect, as losing these will negatively affect the outcome for individuals with an SCI,” explained Dr Ruitenberg.

“That said, the inflammatory response to SCI is very complex, and non-discriminatory suppression of it will not work, and may in fact do more harm than good. For example, our research has demonstrated that some aspects of the inflammatory response are actually good, and we need them for wound healing, but then we also know of others that are bad and becomes non-resolving.”

“So there is something about this type of neurological injury itself that negatively influences the inflammatory response itself and gives you that extra tissue damage.” he added.

“With SpinalCure’s help, we are creating new insights into what type of immune cells are recruited to the injured spinal cord, how they get there, the molecules that they produce, and how they communicate together to influence the recovery process.

“It is very exciting that some of this work has progressed into the clinical trial stage (ACTRN Trial ID 12616001385437),” Dr Ruitenberg said, “and we hope to be able to comment on its outcomes in the not too distant future”.

A/Prof Marc Ruitenberg’s relationship with SpinalCure Australia goes back 2012. (Photo: uq.edu.au)

As explained in his latest research paper, Dr Ruitenberg got a step closer to understanding the inflammatory response to spinal cord injury, and how to
manipulate it.

This study, published here, is the result of eight years of work.

“Undertaking this research was made possible because of the funding from SpinalCure”.

“We discovered that there was a new molecule or  a molecular mechanism that in a way acts as a break on the inflammatory response so what we found is that that molecule is really controlling the way that the immune system is responding to spinal cord injury, and if we manipulate or interfere with that response, we can influence the outcome either positively or negatively”.

Lab data cross-validated with human data

Dr Ruitenberg’s team also cross-validated the lab findings with human data.

“We work very closely with clinicians at Brisbane’s Princess Alexandra er Hospital, which is our main trauma hospital with a dedicated Spinal Injuries Unit. to look at all clinical registry data that is available there This collaboration allowed us to show that the same cells and pathways are activated in human patients.

“[We discovered] that neutrophil mobilisation, one of the most abundant type of immune cells that we have, into the blood (because they are normally stored in reservoirs like the bone marrow), is directly associated with the severity of the injury and also outcomes.

“The extent of that mobilisation response, that response to spinal cord injury, and its influence over outcomes was conserved between human patients and the preclinical mouse studies, which is very strong because we can test direct causality in the lab and have maximum confidence that whatever we are studying in the lab is likely to translate to the human population, and that’s of course very important in that we are not studying a phenomenon that may be not relatable to real patients”.

Insights critical for development of new anti-inflammatory therapies

Generating these insights is critical for the development of new and effective anti-inflammatory therapies that can improve recovery.

“This work is very much discovery-driven, giving us new mechanistic insights, which allows us to develop new drugs, but this is of course very costly and time-consuming,” said Dr Ruitenberg.

“So, what we are also doing is to say, ‘Okay, we may not have the perfect drug sitting on the shelf right now, but what medicines are there that are already out there in clinical use and that we know have an effect on the pathways that we have identified through our research and thus can positively affect recovery from spinal cord injury?”.

“One of the treatments that we came up with this way, was, for example, intravenous immunoglobulin therapy. 

“So that’s a drug that was already in use for other clinical conditions.

We were able to show in the lab, in our animal model, that it is highly effective in treating acute spinal cord injury, and because it’s a drug that is already in use with a good safety profile, then the pathway to medical clinical translation and to hopefully make a fast and real impact into people’s lives becomes very fast.

IVIg is now being used here in Australia to treat new injuries in a world-first clinical trial.

Click here to look at the research paper that made this trial possible.

Finding the funding

Marc says that finding the funding for these kinds of projects is never easy.

“If you want to do really good, highimpact research, particularly in the field of spinal cord injury, it often takes many years or a long time to develop the stories and to do effectively do the things that we need to do to find a cure”.

“If there weren’t organisations like SpinalCure we wouldn’t be able to do what we do, generating the scientific data and the results that we need to give those affected by this terrible condition hope of a better life”.

“The funding is thus vitally important”.

Watch a video update about Dr Ruitenberg’s project.

If you would like to make a tax-deductible donation to life-changing research today – please visit www.spinalcure.org.au/donate.