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Studies give hope for the treatment of spinal cord injuries – ScienceDaily

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Researchers from the University of Birmingham have shown that an existing drug can reduce damage after a spinal cord injury by blocking the inflammatory response in the spinal cord.

Their study, published today in Art Clinical and translational medicinedemonstrates that AZD1236, a drug developed by AstraZeneca, can significantly reduce “secondary damage” caused by the body’s response to spinal cord injury (SCI).

Researchers led by Professor of Neurology Zubair Ahmed, head of the Department of Neurology and Ophthalmology at the University’s Institute of Inflammation and Aging, used animal models to demonstrate that AZD1236 can promote significant nerve regeneration with significant 80% preservation of nerve function. compression injuries of the spinal cord.

Importantly, this resulted in an 85% improvement in movement and sensitivity. These dramatic effects were observed only after three days of AZD1236 treatment, beginning 24 hours after injury. Within three weeks, the animals treated with AZD1236 showed an unprecedented recovery, while the control group still showed a significant deficit six weeks after injury.

One of the key factors in secondary SCI damage is disruption of the blood-spinal barrier (BSCB). This leads to swelling (excessive accumulation of fluid around the spinal cord) and causes an inflammatory reaction that can eventually interfere with 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 involved in inflammatory processes.

The researchers demonstrated that AZD1236 stops the swelling caused by SCI and reduces BSCB destruction and scarring at the site of injury. They also studied the effect of AZD1236 dosing on the activity of MMP-9 and MMP-12 in both the bloodstream and the cerebrospinal fluid surrounding the spinal cord.

Here, they demonstrated significant suppression of enzyme activity both after oral and intrathecal (spinal canal injections). Oral administration reduces the activity of the enzyme in serum by 90% and in cerebrospinal fluid by 69-74%. Not surprisingly, intrathecal injection provided higher levels (88-90%) of suppression in cerebrospinal fluid.

Further studies have shown that AZD1236 suppresses the formation of proinflammatory cytokines (molecules that are known to contribute to the development of prolonged neuropathic pain, which often occurs after SCI) by 85-95%. It has also been found that AZD1236 is 82% more effective in relieving the sensitivity of neuropathic pain to cold, heat and touch caused by SCI, compared to currently used painkillers such as pregabalin (Lyrica) and gabapentin.

Professor Ahmed commented: “There are currently no reparative drugs for patients with SCI, the treatment provides only symptomatic relief and does not address the major molecular mechanisms that cause or contribute to edema and breakdown of the blood and spinal cord barrier. This drug may be the first of its kind. classroom treatment of some of the key pathological factors of SCI and can revolutionize the prospects of recovery of patients with SCI ”.

Hitesh Sangani, Executive Director of Discovery Sciences, AstraZeneca, said: “The work of Professor Ahmed and his team has been supported through our Open Innovation Program and represents a very successful collaboration between academia and industry to provide real benefits to affected SCI patients. an area that has a great medical need. Exploring the potential of AZD1236 for this new indication is a great outcome for our open innovation program and in line with our spirit of “sharing ideas and allowing scientific innovation to cross the boundaries between academia and industry will help to quickly turn innovative ideas into scientific breakthroughs and potential new drugs ».

The University of Birmingham has applied for a patent covering selective combined inhibition or expression of the matrix metalloproteinase MMP-9 (gelatinase B) and MMP-12 (macrophage metalloelastase) after SCI or related neurological tissue damage.

The University of Birmingham Enterprise is now looking for investors and partners to conduct clinical trials of this promising therapeutic tool.

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Materials provided University of Birmingham. Note: Content can be edited by style and length.

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