Research from the University of Birmingham in the UK has indicated that a cancer therapy could help damaged nerves repair themselves following spinal injury.
The research shows that AstraZeneca’s candidate drug AZD1390 can block the response to DNA damage in nerve cells and promote regeneration of damaged nerves, restoring sensory and motor function after spinal injury.
A previous study from the same research team investigating another of AstraZeneca’s drug candidates (AZD2136) showed that it could reduce damage after spinal cord injury, by blocking the inflammatory response.
The initial study1 of AZD1390 found that it stimulated nerve cell growth in culture, and inhibited the ATM protein kinase pathway – a critical biochemical pathway regulating the response to DNA damage.
The candidate, which was used in animal models, showed that oral treatment of it resulted in the suppression of the ATM protein kinase pathway, nerve regeneration beyond the site of injury, and the ability of these nerves to carry electrical signals across the site of the injury.
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 DNA Damage Response system (DDR) is activated by DNA damage, including DSBs in the genome, which occur in several common cancers and also after spinal cord injury.
Author of the study, Professor Zubair Ahmed, from the University of Birmingham Institute of Inflammation and Ageing, said: “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 four weeks of injury.”
Co-author, Dr Richard Tuxworth from the Institute of Cancer and Genomic Sciences 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.”
References
1: Ahmed Z, Tuxworth RI. The brain penetrant ATM inhibitor, AZD1390, promotes axon regeneration and functional recovery in preclinical models of spinal cord injury. Clin Transl Med. 2022;4(6):eaat1719. doi:10.1002/ctm2.962
