Study: Cancer drug candidate helps regenerate nerves after spinal injury

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British scientists say a drug in development as a cancer therapy can help regenerate damaged nerves after spinal trauma. Photo by magicmine

An investigational cancer drug has been shown to help regenerate damaged nerves after spinal trauma with “remarkable recovery” of sensory and motor functions in animals, British scientists say.

The researchers said they used cell and animal models to demonstrate that oral treatment with a cancer candidate drug — known as AZD1390 and manufactured by AstraZeneca — could block the response to DNA damage in nerve cells and promote regeneration of damaged nerves.

This, investigators from the University of Birmingham in England said, helped restore sensory and motor function after spinal injury. Their research letter was published Tuesday in Clinical and Translational Medicine.

“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,” Zubair Ahmed, professor of neuroscience at the university and lead author of the research letter on AZD1390, said in a news release.

The persistent activation of the body’s DNA damage response system may prevent recovery from spinal cord injury, Ahmed noted. So, he said, blocking it with a drug such as AZD1390 could promote nerve repair and help restore function after injury.

Ahmed is also lead for the neuroscience and ophthalmology section in the University of Birmingham’s Institute of Inflammation and Aging.

The scientists said they anticipate a swift timeline toward further research and practical application of their initial findings.

Ahmed’s colleague, Richard Tuxworth from the University of Birmingham’s Institute of Cancer and Genomic Studies, who co-authored the research letter, said in the news release that “repurposing this existing investigational drug potentially means we can reach the clinic significantly faster than developing a new drug from scratch.”

AZD1390, described as a potent, “brain-penetrating” ataxia telangiectasia mutant kinase inhibitor, is under investigation in a federally funded, multi-center phase 1 trial in the United States and United Kingdom for brain tumor treatment, looking at whether it safely and effectively sensitizes cancer cells to radiation therapy. The trial is expected to end in May 2024.

The drug also has investigational status in England.

In the new study, the researchers first found that AZD1390 stimulated nerve cell growth in culture, and inhibited the ATM protein kinase pathway that regulates the response to DNA damage, according to the news release.

Next they used animal models to investigate the effect of AZD1390 following spinal cord injury and found that oral treatment with the drug “resulted in significant 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.”

AstraZeneca, which is based in the United Kingdom, provided AZD1390 to the researchers for their study through its Open Innovations program.

The program is described as sharing compounds, tools, technologies and expertise with the scientific community to advance drug discovery and development.

In May, the scientists published a study in the same journal on another AztraZeneca drug, AZD1236, which they found may significantly reduce “secondary damage” after spinal trauma by blocking the inflammatory response in the spinal cord.

That study also was funded by AstraZeneca’s Open Innovations program.

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