New Study Reveals Hope for Recovery of Patients with Spinal Cord Injury

Spinal Cord Injury or SCI is a medical condition caused due to damage to the spinal cord as a whole or to any of its vertebrae, ligaments or disks. Such damage can be caused due to a sudden blow to the spine that fractures, dislocates, crushes, or compresses one or more vertebrae. Car crashes are the leading cause of SCI among people younger than 65 whereas falls cause most SCIs in persons aged 65 and older. 

In a recent study scientists at the University of Birmingham have shown that an existing drug AZD1236 (developed by AstraZeneca) may reduce ‘secondary damage’ by blocking the inflammatory response post spinal cord injury (SCI). The research, published in Clinical and Translational Medicine, was led by Professor Zubair Ahmed, Professor of Neuroscience and lead for the Neuroscience and Ophthalmology Section at the University’s Institute of Inflammation and Ageing. 

SCI – A Cascade Process Leading to Nerve Cell Death

In the event of SCI, inflammation occurs at the spinal cord region, thus cutting off the vital blood supply to the nerve tissue and starving it of oxygen. This in turn sets off a cascade of devastation that affects the entire body, causing the injured spinal tissue to die, be stripped of its insulation, and be further damaged by a massive response of the immune system. 

One of the key drivers of SCI secondary damage is breakdown of the blood-spinal cord barrier (BSCB) resulting in oedema (excess fluid build-up around the spinal cord) and triggering an inflammatory response that can ultimately hinder the healing process, eventually leading to nerve cell death.

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AZD1236 and Its Mode of Action

AZD1236 is a potent and selective inhibitor of two enzymes, matrix metalloprotease (MMP)-9 and MMP-12 implicated in the inflammatory pathway. In the article, the researchers demonstrate that AZD1236 halts SCI-induced oedema, reducing the blood-spinal cord barrier (BSCB) breakdown and scarring at the site of the injury. The researchers used animal models to show that AZD1236 can promote significant nerve regeneration, with a dramatic 80% preservation in nerve function following spinal cord compression injury. 

While AZD1236-treated animals showed unprecedented recovery within three weeks, the non-treated controls showed significant deficits even at six weeks post-injury. Usage of AZD1236 was seen to suppress the activity of enzymes involved in the inflammatory pathway (MMP-9 and MMP-12) in both the bloodstream and cerebrospinal fluid. When orally administered AZD1236 significantly reduced enzyme activity in the serum (by 90%). 

The study also showed that administration of AZD1236 resulted in 85-95% suppression of cytokines which play an important role in causing inflammation in SCI patients. Compared to the presently used medication such as pregabalin (Lyrica) and gabapentin, the drug was found to be 82% more effective at reducing pain sensitivity.

Could AZD1236 Be a Glimmer of Hope for Recovery From SCI?

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.”

Author

Arvind C. Shekhar

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