A drug under investigation as a cancer treatment has shown exciting promise in a rather different branch of medical research, with scientists demonstrating how it can promote nerve repair following spinal injury. The breakthrough shows how the drug acts on a DNA damage response mechanism at play in both these unrelated conditions, and triggers a "remarkable" recovery in mice with injured spinal cords.
Led by scientists at the University of Birmingham, the research focused on an experimental drug called AZD1390. This drug is under investigation as a cancer therapy due its potential to make tumor cells more sensitive to radiation treatment. It does so by penetrating the brain and inhibiting a mechanism linked to DNA damage, called the ATM protein kinase pathway.
This is implicated in what the authors call the DNA Damage Response system, which swings into action in response to DNA damage caused by several common cancers, and also in response to spinal cord injury. The authors of the new study hypothesize that the activation of this system may slow or prevent recovery from spinal cord injury, by hampering nerve repair. The thinking was that by using AZD1390 to inhibit the ATM signaling pathway, they could clear the way for the growth of new nerve cells.
To begin with, the experiments centered on nerve cells in culture. AZD1390 was found to stimulate new growth in this environment and inhibit the ATM protein kinase pathway. In mice with spinal cord injuries, oral administration of AZD1390 was also shown to significantly suppress the pathway. Further, it promoted nerve regeneration beyond the site of the injury, and enhanced the capacity of these nerves to relay electrical signals. The restoration of sensory and motor function was "dramatic," the team writes in the research paper.
“This is an exciting time in spinal cord injury research with several different investigational drugs being identified as potential therapies for spinal cord injury," said study author Professor Zubair Ahmed. "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."
Such a rapid and effective recovery, making injured mice appear much like uninjured mice in such a short time frame, positions AZD1390 as an exciting potential treatment for a condition that has no cure. Though just an initial study, the fact that it centers on a drug already under investigation may also shorten its path to clinical use.
“This early study shows that AZD1390 could be used as a therapy in life-changing conditions," said study author Dr Richard Tuxworth. "In addition, repurposing this existing investigational drug potentially means we can reach the clinic significantly faster than developing a new drug from scratch."
The research was published in the journal Clinical and Translational Medicine.
Source: University of Birmingham
