A group of UK-based researchers at the University of Birmingham have potentially identified a powerful new spinal cord injury treatment, discovering that an existing drug may mitigate damage from the condition.
In an animal model study, the University of Birmingham team observed that the drug AZD1236 – developed by AstraZeneca – can reduce secondary damage after a spinal cord injury (SCI) caused by the body’s inflammatory response. The researchers found that AZD1236 significantly enhanced nerve regeneration, preserving a staggering 80% of nerve functioning following spinal cord compression injury.
After just three days of the spinal cord injury treatment, there was an 85% improvement in movement and sensation, with the effects starting in just 24-hours post-injury. Furthermore, after three weeks of being administered AZD1236, the animals displayed remarkable recovery, whereas the control animals showed considerable deficits at six weeks post-injury.
The study findings are published in Clinical and Translational Medicine.
The global SCI landscape
A spinal cord injury is caused when the spinal cord suffers damage and is predominantly caused by trauma, such as car accidents or falls, or through disease and degeneration, such as cancer. Estimates from the World Health Organization suggest that worldwide, between 250,000 and half a million people experience a spinal cord injury each year, with 40 to 80 cases per million.
Spinal cord injury patients have a high mortality rate, with the first year post-injury being the highest. SCI patients are two to five times more likely to die prematurely than those without an SCI, and survival rates are lowest in low- and middle-income countries. The condition can have devastating impacts on the patient, causing social and economic barriers, depression, and additional health complications. Moreover, current spinal cord injury treatment options are currently inadequate.
A groundbreaking spinal cord injury treatment
One of the principal drivers of secondary damage is caused by the breakdown of the blood-spinal cord barrier (BSCB), consequently leading to excess fluid build-up around the spinal cord (oedema). This process triggers an inflammatory response that mitigates the healing process and results in the death of nerve cells. In their investigation, the scientists ascertained that AZD1236 is an effective and selective inhibitor of MMP-9 and MMP-12, essential enzymes in the inflammatory process.
The team exhibited that the spinal cord injury treatment prevents oedema and reduces BSCB breakdown and scarring at the injury site. Additionally, they analysed how AZD1236 dosing impacted MMP-9 and MMP-12 in the bloodstream and cerebrospinal fluid surrounding the spinal cord. AZD1236 inhibited enzyme activity by 90% in serum and 69-74% in the cerebrospinal fluid in oral dosing, whereas through intrathecal dosing, the treatment delivered 88-90% suppression in the cerebrospinal fluid.
Their analysis illuminated that AZD1236 suppressed the development of cytokines that cause inflammation by 85-95%. The treatment was also 82% effective at reducing SCI-induced neuropathic pain sensitivity to cold, heat and touch compared to traditional pain relief drugs, pregabalin and gabapentin.
Professor Zubair Ahmed, Professor of Neuroscience and lead for the Neuroscience and Ophthalmology Section at The University’s Institute of Inflammation and Ageing, 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. 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”.
Hitesh Sanganee, Executive Director, Discovery Sciences, AstraZeneca, said: “The work by Professor Ahmed and his team has been supported through our Open Innovation Programme and represents a very successful collaboration between academia and industry to bring about the possibility of real benefits to patients affected by SCI, an area of great medical need. Exploring the potential of AZD1236 for this new indication represents a great outcome for our Open Innovations programme and aligns with our ethos of sharing ideas and enabling scientific innovation to cross boundaries between academia and industry will help to translate innovative ideas into scientific breakthroughs and potential new medicines more quickly.”
Future developments
The University of Birmingham researchers are now looking for investors and partners to support a spinal cord injury treatment clinical trial. They have also filed a patent application covering selective combined inhibition activity or expression of both MMP-9 and MMP-12 after SCI or related injury to neurological tissue.
