The hopes of patients suffering very different diseases may rest with a single drug. Already showing encouraging signs of increasing the effectiveness of treatments for brain cancer, the drug AZD1390 has now excelled in preclinical trials for restoring motion after spinal injuries, which could mean that many may no longer need to use wheelchairs.
Even more remarkably, AZD1390 can be taken orally, a paper in Clinical and Translational Medicine reports. That greatly widens the pool of people who could gain access to medication without needing daily visits to hospitals.
Research is still at an early stage, with clinical trials being needed to assess safety and effectiveness under real-world conditions. The first half of these is underway in the form of cancer trials. Studies of spinal repair are so far limited to cell cultures, mice, and rats, but the success in animals is impressive.
Fighting cancers and repairing damaged nerves may not seem to have a lot in common to most of us. What brings them together are DNA double-strand breaks. As the name suggests, these involve severing both strands of the DNA double helix at once, creating a danger of rearrangements in the genome. The body's response to double-strand breaks is to try to repair them. Although in most circumstances this is beneficial, indeed essential, under certain circumstances it can do more harm than good, and this is where AZD1390 may come in.
AZD1390 is being investigated by AstraZeneca for its capacity to block ataxia-telangiectasia mutated (ATM) – a protein activated by double-strand breaks for DNA repair. As crucial as ATM is for cancer suppression, targeted blocking of its activity is being studied to make cancer cells more sensitive to radiotherapy.
Similarly, over-activation of the repair system is suspected to prevent recovery of the central nervous system after spinal injury. This is why Professor Zubair Ahmed of the Unversity of Birmingham and team thought AZD1390 might prove beneficial for recovery from spinal damage. The paper provides support for the idea, with injured animals taking just four weeks on AZD1390 to regain capacities identical to uninjured controls.
"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,” Ahmed said in a statement.
The team also hope safety trials run for cancer treatments will give them a headstart, speeding the path to the drug's clinical use for spinal injuries.
The same team also tested another drug, KU-60019. Although it produced similar nerve growth in cell cultures to AZD1390, KU-60019 had no effect when taken orally, marking a significant disadvantage.
Less than two months ago the same team published evidence for nerve regeneration in animals using a different drug, AZD1236, also developed by AstraZeneca.
