Scientists demonstrated that AZD1236 halts oedema while reducing spinal cord breakdown at the site of the injury
Research from the University of Birmingham has shown that an existing drug may reduce damage following spinal cord injury by blocking the inflammatory response in the spinal cord.
The scientists demonstrated that AZD1236, a drug developed by AstraZeneca, can significantly reduce secondary damage caused by the body’s response to spinal cord injury (SCI).
The researchers – led by Professor Zubair Ahmed, Professor of Neuroscience at The University Institute of Inflammation and Ageing – used animal models to demonstrate that AZD1236 can promote significant nerve regeneration, with an 80% preservation in nerve functioning, following spinal cord compression injury.
This translated into an 85% improvement in movement and sensation, and these dramatic effects were observed following only three days of treatment, with a course of AZD1236 starting within 24 hours of the injury. Within three weeks AZD1236-treated animals showed unprecedented recovery, while controls still showed significant deficits at six weeks post-injury.
One of the key drivers of SCI secondary damage is breakdown of the blood-spinal cord barrier (BSCB). This results in oedema – excess fluid build-up around the spinal cord – and triggers an inflammatory response that can hinder the healing process, and lead to nerve cell death.
AZD1236 is a potent and selective inhibitor of two enzymes – MMP-9 and MMP-12 – which are implicated in the inflammatory process. The scientists demonstrated that AZD1236 halts SCI-induced oedema, while reducing BSCB breakdown and scarring at the site of the injury. They also examined the effect of AZD1236 dosing on MMP-9 and MMP-12 activity in both the bloodstream and cerebrospinal fluid which surrounds the spinal cord.
Professor Ahmed commented: “There is currently no reparative drug available for SCI patients, treatments only provide symptomatic relief and do not tackle the underlying molecular mechanisms that cause or contribute to oedema and blood-spinal cord barrier breakdown.”
He added: “This drug has the potential to be a first-in-class treatment against some of the key pathological drivers of SCI and could revolutionise the prospects for recovery of SCI patients.”