A candidate cancer drug currently in development has been also shown to stimulate regeneration of damaged nerves after spinal trauma. Four weeks after spinal cord injury, animals treated with the candidate drug, AZD1390, were “indistinguishable” from uninjured animals, according to the researchers.
The study, published in Clinical and Translational Medicine, demonstrated in cell and animal models that the candidate drug, AZD1390, can block the response to DNA damage in nerve cells and promote regeneration of damaged nerves. This restored sensory and motor function after spinal injury.
The announcement comes weeks after the same research team showed a different investigational drug, AZD1236, can reduce damage after spinal cord injury, by blocking the inflammatory response.
AZD1390 is also under investigation by AstraZeneca to block ATM-dependent signalling and repair of DNA double strand breaks (DSBs), an action which sensitises cancer cells to radiation treatment. The ATM protein kinase pathway – a critical biochemical pathway regulating the response to DNA damage. The DNA Damage Response system (DDR) is activated by DNA damage, including DSBs in the genome, which also happen in several common cancers and also after spinal cord injury.
Professor Zubair Ahmed, from the University’s Institute of Inflammation and Ageing and Dr Richard Tuxworth from the Institute of Cancer and Genomic Sciences hypothesised the persistent activation of this system may prevent recovery from spinal cord injury, and that blocking it would promote nerve repair and restore function after injury.
Their initial studies found that AZD1390 stimulated nerve cell growth in culture, and inhibited the ATM protein kinase pathway – a critical biochemical pathway regulating the response to DNA damage.
AZD1390 was tested in animal models following spinal cord injury. Oral treatment with AZD1390 significantly suppressed the ATM protein kinase pathway, stimulated nerve regeneration beyond the site of injury, and improved the ability of these nerves to carry electrical signals across the injury site.
Professor Ahmed commented: “This is an exciting time in spinal cord injury research with several different investigational drugs being identified as potential therapies for spinal cord injury. We are particularly excited about AZD1390 which can be taken orally and reaches the site of injury in sufficient quantities to promote nerve regeneration and restore lost function.
“Our findings show a remarkable recovery of sensory and motor functions, and AZD1390-treated animals being indistinguishable from uninjured animals within 4 weeks of injury.”
Dr Tuxworth added: “This early study shows that AZD1390 could be used as a therapy in life-changing conditions. In addition, repurposing this existing investigational drug potentially means we can reach the clinic significantly faster than developing a new drug from scratch.”
Source: University of Birmingham
