An experimental drug capable of entering the brain can promote the regeneration of nerves that have been damaged by spinal injury. Currently this drug – called AZD1390 – is being developed to treat cancer, but researchers at the University of Birmingham have proven its effectiveness in repairing the damage caused by spinal trauma.
When taken orally, this drug can block the response to DNA damage in nerve cells and encourage damaged nerves to regenerate, thereby restoring sense and motor function after spinal injury, according to it has been demonstrated in a study published in Clinical and Translational Medicine in which cell and animal models were used.
A few weeks ago, the same group of scientists showed that another investigational drug – AZD1236 – can reduce the damage caused by spinal cord injury by blocking the inflammatory response. Both investigations have been supported by AstraZeneca’s Open Innovations Program, which shares compounds, tools, technologies and expertise with the scientific community to advance drug discovery and development.
A potential new treatment for spinal cord injuries
Professor Zubair Ahmed, from the University’s Institute of Inflammation and Aging, and Dr Richard Tuxworth, from the Institute of Cancer and Genomic Sciences, hypothesized that persistent activation of the DNA damage response (DDR) system may prevent recovery from spinal cord injury, so blocking it would boost nerve repair and restore function after injury.
“Our findings show a remarkable recovery of sensory and motor functions in animals treated with AZD1390 after spinal cord injury”
They initially found that AZD1390 stimulated the growth of nerve cells in culture and inhibited the ATM protein kinase pathway, a key biochemical pathway responsible for regulating the response to DNA damage. These scientists then used animal models to study the effect of AZD1390 after spinal cord injury and showed that treatment with oral AZD1390 resulted in significant suppression of the ATM protein kinase pathway, the regeneration of nerves more beyond the injured area and the ability of these nerves to transmit electrical signals through the site of injury.
“This is an exciting time in spinal cord injury research with several different investigational drugs identified as potential therapies for spinal cord injuries. We are particularly excited about AZD1390, which can be taken orally and reaches the site of injury in sufficient amounts to promote nerve regeneration and restore lost function,” said Professor Ahmed. “Our findings show a remarkable recovery of sensory and motor functions, and AZD1390-treated animals cannot be distinguished from uninjured animals within four weeks of injury.”
Dr Tuxworth added: “This initial study shows that AZD1390 could be used as a therapy in life-changing conditions. Furthermore, repurposing this existing investigational drug potentially means we can get to the clinic much faster than developing a new drug from scratch.” In fact, the University of Birmingham Enterprise has already filed a patent application on the inhibition of the ATM/Chk2 DNA damage response pathway by compounds such as AZD1390, which could become a possible therapeutic option to promote nerve repair.
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