World first research a game changer for spinal cord injuries
TRI-based Mater Research Principal Fellow, Professor Jean-Pierre Levesque, is leading an international collaboration to develop new treatments for neurogenic heterotopic ossifications (NHO)—an extremely debilitating complication of spinal cord injuries.
The project is being funded through a US Department of Defense (DoD) Spinal Cord Injury Research Program – Expansion Award grant.
First observed in battlefield-injured soldiers during World War One, today NHO affects 1 in 5 people with spinal cord injuries (SCI). It is even more prevalent in soldiers with SCI, affecting up to 60 per cent of cases.
It involves the formation of bones in soft tissues outside the skeleton. These malformed bones usually grow around joints such as the knee, hip, elbow or shoulder. They start to develop within weeks of the injury and can become so large (up to 2 kg) that patients can no longer bend their joints, which become encased in bone. These bones can also entrap large blood vessels and nerves, which contribute to increasing pain and paralysis.
Professor Levesque says there is no effective treatment to prevent or stop the formation of these bones.
“The only treatment is complicated surgical removal and even after this, the bones can still grow back, requiring another surgery to remove them again,” he says.
With the DoD grant, Professor Levesque will conduct the world’s first prospective study into NHO. His aim is to develop new treatments to stop these bones from growing and predict which patients are most likely to develop the condition, so they can commence treatment straight away.
“A few years ago, we successfully developed a pre-clinical model to replicate SCI associated NHO and discovered that heterotopic bones only develop when there is an injury of the central nervous system combined with muscular trauma,” says the Professor.
“We also discovered that NHO is driven by a type of white blood cell, called a macrophage, which stimulates the formation of heterotopic bones instead of muscle repair.
“From our previous research projects, we know a stress response from the spinal cord injury leads to the release of a stress hormone into the blood which directly promotes NHO development.
“In this new Mater research, we will explore how this stress response, excessive inflammation and infectious microbes combine to enhance NHO, and determine whether combining medicines that block the stress hormone and inflammation can prevent NHO development.
“We also aim to validate our findings in people with SCI, which if successful will result in the development of biomarkers to predict early NHO development.”
Professor Levesque is teaming up with Professor Genet, Head of the Rehabilitation and Physical Medicine Department at Raymond Poincaré Hospital near Paris, the main referring hospital in Paris region for victims of spinal cord and brain injuries.
The Hospital treats about a 100 new SCI patients each year.
“If successful, this research will be life-changing for affected patients and their caregivers. These new treatments will vastly improve patients’ everyday lives as maintaining joint mobility allows them to progress through rehabilitation. They will also reduce the need for long and complicated surgeries to remove these unwanted bone,” says Professor Levesque.
“If our experiments confirm the efficacy of selected drugs to reduce the development of NHOs in laboratory models this could be rapidly translated into pilot clinical trials in Brisbane and Paris, as the selected drugs are already well characterised and used in patients to treat other inflammatory diseases.”
This story was first published by Mater Research. Photo of Professor Levesque courtesy of Mater Research.
