Unprecedented Recovery: Drug Helps Treat Spinal Cord Injuries

Researchers discovered that AZD1236, a drug developed by AstraZeneca, might reduce damage after spinal cord injury.

New hope for spinal cord injury treatment

Scientists from the University of Birmingham found that suppressing the inflammatory response in the spinal cord may minimize damage following spinal cord injury.

Their findings, recently published in Clinical and Translational Medicine, show that AZD1236, an AstraZeneca medicine, may considerably reduce ‘secondary damage’ produced by the body’s response to spinal cord injury (SCI).

Animal models were used by researchers led by Professor Zubair Ahmed, Professor of Neuroscience and Section Lead for the Neuroscience and Ophthalmology Section at The University’s Institute of Inflammation and Ageing, to demonstrate that AZD1236 can promote significant nerve regeneration, with a dramatic 80% preservation in nerve function following spinal cord compression injury.

Crucially, this translated into an 85% improvement in movement and sensation. These dramatic effects were observed following only three days of treatment with AZD1236, starting within 24 hours post-injury. Within three weeks, the 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 the 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 ultimately 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 researchers demonstrated that AZD1236 halts SCI-induced oedema, and reduces 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.

Here they demonstrated significant suppression of enzyme activity after both oral dosing, and intrathecal dosing (injection into the spinal canal). Oral dosing reduced enzyme activity by 90% in serum, and 69-74% in the cerebrospinal fluid. Unsurprisingly, intrathecal injection delivered higher levels (88-90%) of suppression in the cerebrospinal fluid.

Further studies showed that AZD1236 suppressed the formation of pro-inflammatory cytokines (molecules that are known to contribute to the development of long-lasting neuropathic pain, which often follows SCI) by 85-95%. AZD1236 was also found to be 82% more effective at alleviating SCI-induced neuropathic pain sensitivity to cold, heat, and touch when compared to currently used pain medications such as pregabalin (Lyrica) and gabapentin.

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. This drug has the potential to be a first-in-class treatment against some of the key pathological drivers of SCI and could revolutionize 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 program 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.”

The University of Birmingham Enterprise has filed a patent application covering selective combined inhibition activity or expression of both matrix metalloproteinase MMP-9 (gelatinase B) and MMP-12 (macrophage metalloelastase) after SCI or related injury to neurological tissue.

The University of Birmingham Enterprise is now seeking investors and partners to take this promising therapeutic to clinical trials.

Reference: “Clinic-ready inhibitor of MMP-9/-12 restores sensory and functional decline in rodent models of spinal cord injury” by Zubair Ahmed, Sharif Alhajlah, Adam M. Thompson and Rebecca J. Fairclough, 20 May 2022, Clinical and Translational Medicine.
DOI: 10.1002/ctm2.884

DrugsNerve CellsPopularSpinal CordUniversity of Birmingham
Comments ( 14 )
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  • Jennifer Parsons

    Following successful decompression surgery in 2016 at occipital level and fusion of C1 2 and 3 I suffer from Allodynia and neuropathic pain. Interested in your findings .

  • Ray Fee

    It’s horrific to treat other species like this.

  • Sherry Scott

    I have numerous things wrong with my spine: degenerative disease in my neck, nerve damage throughout my back, neck, butt, legs, feet, arms and legs, sciatica, scoliosis, and my tailbone is shifted making it hard to sit – amongst other problems caused by such ailments. Not to mention – carpal tunnel in both hands, left shoulder repeatedly dislocated – 12th time required surgery to sew muscle and tissues back in place, head trauma, broke both lower bones in right arm, hurt both knees at different times resulting twice on crutches, and numerous accidents that were not my fault but still could not collect a dime for any type of compensation! I would love 💘 to find something that would take the pain, numbness, and burning feelings away! Most nervous about pharmaceuticals though, so I would definitely need to see the pros and cons. What we really need is something that works and is as natural as possible!

  • Sherry Scott

    Keep me posted please!!!

  • Mary L. Migliore

    I have Klippel Feil Syndrome. I have had Sergey and am unable to walk. This could be very helpful to Me. I need to walk again and take care of my home. Anything that can help Me, would be appreciated.

  • David padgett

    As a t12 incomplete person I am very interested in your findings and would like to be part of human testing when approved . it may or may not heal me but I noticed it can be used more affective for pain management than lyrica and I really am interested in that aspect for at least being able to live without pain everyday would be a blessing . Please contact me asap I would love to learn more .

  • Gary Peterson, MArch, PhD

    I’d like to know if AZD1236 could help repair the degenerative effects of Post Polio (PPS).

  • Randy

    Would love to hear updates on this new treatment. Had to go on Disability many yrs ago. Went through the pharmacy nightmare of getting pain meds only to have them taken away. Last time I told them I was done being yanked around. Keep me posted. If this is true it’s an answer to prayer.

    • Larry White

      I have an incomplete spinal cord injury at the t3 and t4 they were fused together. This from a car accident. I walk with a walker but my back is experiencing pain so bad that I can’t walk for very long without cramping. I’m 72 but would love to take part in any study of the drug. In

  • Michele Smith

    I had a partial spinal cord injury 4 years ago. In which I incurred a severe contusions to my T11 T12 and L4 vertebra. I have been trying to improve my muscle strength in my legs ever since. I was in rehab for 3 1/2 months before I could walk at all. This is incredible news and something many people will celebrate. I hope the is more progress on this and that it is reasonably priced. To be available for all who need the relief that this will no doubt achieve.

  • Satendra chaurasia

    As a t12 l1 incomplete person I am very interested in your findings and would like to be part of human testing when approved . it may or may not heal me but I noticed it can be used more affective for pain management than lyrica and I really am interested in that aspect for at least being able to live without pain everyday would be a blessing . Please contact me asap I would love to learn more .

  • Satendra chaurasia

    As a t12 KE incomplete person I am very interested in your findings and would like to be part of human testing when approved . it may or may not heal me but I noticed it can be used more affective for pain management than lyrica and I really am interested in that aspect for at least being able to live without pain everyday would be a blessing . Please contact me asap I would love to learn more .

  • Larry White

    I have an incomplete spinal cord injury at the t3 and t4 they were fused together. This from a car accident. I walk with a walker but my back is experiencing pain so bad that I can’t walk for very long without cramping. I’m 72 but would love to take part in any study of the drug.

  • Jacquline Myers

    I am T12/L1 incomplete, 5 years July 5th.
    I have hurt for 5 years also, with sheer grit I slung my legs to walk. By the grace of God! A new neurosurgeon finally found the problem with a MRI & MYELOGRAM- They had overlooked a nerve sticking through a hole in my spinal it had become overgrown in scar tissue. The pain was indescribable. They called it a tethered spinal cord-well it had to be untethered. After that surgery the nerve damage is worse. I never knew pain existed on this level. Today I sit here with a spinal cord stimulator in 5 days that will be removed. I my surgery to implant will be august 8th. Durning that time I will have nothing for nerve pain! I am terrified it will be pure suffering!!!! I plan to recovery God willing!!! I would love to participate in your testing when approved. The man that finds a cure for spinal cord injuries will be a hero for all who suffer. I know it will not be long now. Find the cure, God speed!!! People are suffering it is a painful injury. Consider me for a participant please.
    FIND THAT CURE!!!!