Potential cancer drug could help repair spinal injuries shows study

Researchers at the University of Birmingham in the U.K. have shown that a drug being trialed to treat cancer can also help regenerate damaged nerves in case of a spinal injury, a university press release said. 

The process of drug discovery is a long one, with estimates suggesting that as many as 90 percent of candidates fail to make it through the clinical trial process. This has prompted pharmaceutical companies to find other applications for drugs that have already been approved or are near approval. 

When researchers come across similar modes of treatment for a disease, they try drugs that could potentially work in those scenarios to avoid the long route of new drug discovery. The DNA Damage Response system (DDR) is one such system that is activated when the DNA in the cells is damaged. DNA damage can be induced either due to the progression of certain types of cancers or injuries to the spinal cord. 

How did the researchers link the two? 

Professor Zubair Ahmed and Richard Tuxworth both work at the University of Birmingham. However, Ahmed's research interests are Inflammation and Ageing, while Tuxworth works in the fields of cancer and genomic sciences. Working across departments and fields, the duo hypothesized that persistent activation of the DDR system could be responsible for the prevention of healing of a spinal cord injury, and blocking this mechanism could restore nerve repair and function. 

To test their hypothesis, the researchers conducted their experiments with AZD 1390, a candidate drug from AstraZeneca that can cross the blood-brain barrier and block the repair of DNA damage in nerve cells. AZD 1390 works by blocking the ATM protein kinase pathway, critical in regulating the response to DNA damage.

Researchers use this method to sensitize cancerous cells to radiation treatment. This time around, they blocked it to determine if it improved nerve repair.   

What did the researchers find? 

In the studies conducted on nerve cells in a growth medium, the drug inhibited the ATM proteinase kinase pathway and stimulated nerve cell growth. They then tested the drug in animal models where oral administration of the compound showed significant suppression of the pathway, nerve regeneration beyond the site of the injury, and the ability of the nerve cells to carry electric signals across the injury site.

"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 Ahmed in the press release." Our findings show a remarkable recovery of sensory and motor functions, and AZD1390-treated animals being indistinguishable from uninjured animals within 4 weeks of injury."

"This early study shows that AZD1390 could be used as a therapy in life-changing conditions," added Tuxworth. "Repurposing this existing investigational drug potentially means we can reach the clinic significantly faster than developing a new drug from scratch." 

The findings of the study were published in the journal Clinical and Translational Medicine.