AZD1236 Investigational Drug Fosters Nerve Repair After Spinal Injury

Author: University of Birmingham
Published: 2022/07/12 - Updated: 2025/02/22
Publication Details: Peer-Reviewed, Research, Study, Analysis
Topic: Spinal Cord Injury (SCI) - Publications List

Page Content: Synopsis - Introduction - Main - Insights, Updates

Synopsis: This report dives into groundbreaking research on AZD1390, a drug originally developed as a cancer therapy, showing its potential to help repair nerves after spinal cord injuries. It explains how scientists used cell and animal studies to discover that this oral medication can block DNA damage responses in nerve cells, encouraging nerve regeneration and restoring sensory and motor functions. The findings are exciting because they suggest a new way to tackle a condition that often leaves people with lasting disabilities, offering hope to those affected, including seniors or anyone facing mobility challenges. It's particularly interesting since the drug is already in development, which could speed up its availability for spinal injury treatment. This makes it a valuable read for anyone curious about advances in medical science that could improve quality of life for people with spinal cord injuries. - Disabled World (DW).

Introduction

Scientists from the University of Birmingham have shown that a brain-penetrating candidate drug currently in development as cancer therapy can foster regeneration of damaged nerves after spinal trauma.

Focus

The research, published in Clinical and Translational Medicine, used cell and animal models to demonstrate that when taken orally, the candidate drug, known as AZD1390, can block the response to DNA damage in nerve cells and promote regeneration of damaged nerves, so restoring sensory and motor function after spinal injury.

The announcement comes weeks after the same research team showed a different investigational drug (AZD1236) could reduce damage after spinal cord injury by blocking the inflammatory response. Both studies were supported by AstraZeneca's Open Innovations Programme, which shares compounds, tools, technologies, and expertise with the scientific community to advance drug discovery and development.

AZD1390 is also under investigation by AstraZeneca to block ATM-dependent signaling and repair DNA double-strand breaks (DSBs), an action that sensitizes 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 after spinal cord injury.

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Professor Zubair Ahmed from the University's Institute of Inflammation and Ageing and Dr. Richard Tuxworth from the Institute of Cancer and Genomic Sciences hypothesized the persistent activation of this system might 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.

The researchers then used animal models to investigate the effect of AZD1390 following spinal cord injury. Here they showed that oral treatment with AZD1390 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 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 four 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."

University of Birmingham Enterprise has filed a patent application covering inhibition of the ATM/Chk2 DNA damage response pathway by compounds such as AZD1390, which may represent a potential therapeutic strategy to foster nerve repair.

Insights, Analysis, and Developments

The idea of using AZD1390 for spinal cord injuries shows how smart thinking in science can turn an existing drug into something life-changing. Right now, the results come from animal studies, so there's still a lot of work to do to make sure it's safe and effective for people. Even so, this research is a bright spot for anyone affected by these injuries, proving why we need to keep supporting medical studies. It's a step that could open new doors for treatment and give hope to those living with disabilities

Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by University of Birmingham and published on 2022/07/12, this content may have been edited for style, clarity, or brevity. For further details or clarifications, University of Birmingham can be contacted at birmingham.ac.uk NOTE: Disabled World does not provide any warranties or endorsements related to this article.