Canine study suggests neurotoxin monitoring could be used to personalise spinal cord injury treatment

180

Researchers have developed a urine test revealing the presence of a neurotoxin that likely worsens the severity and pain of spinal cord injuries. According to the authors, this could lead to a new treatment tool.

The neurotoxin—acrolein—is produced within the body after nerve cells are damaged, increasing pain and triggering a cascade of biochemical events thought to worsen the injury’s severity. The new test detected the toxin’s presence in dogs that had naturally sustained spinal cord injuries. The injuries were acute, when treatment to reduce acrolein might help prevent further damage.

The researchers studied the presence of a chemical compound called 3-hydroxypropyl mercapturic acid (3-HPMA), a metabolic product of acrolein.

“This has implications for a potential treatment to hinder further damage and reduce pain in people with spinal cord injuries,” says Riyi Shi, a professor of neuroscience and biomedical engineering in Purdue University’s Department of Basic Medical Sciences, College of Veterinary Medicine and Weldon School of Biomedical Engineering, West Lafayette, USA. “Urine 3-HPMA could be used as a biomarker in future clinical trials to non-invasively measure the effect of therapeutic intervention by reducing acrolein after acute spinal cord injury.”

Findings are detailed in a research paper published online in The Veterinary Journal.

The concentration of acrolein can be reduced using the drug hydralazine, which has been approved by the US Food and Drug Administration for hypertension. The drug has been shown to reduce acrolein and pain following spinal cord injury in laboratory rats and mice.

In the new study, urine was studied from 10 dogs with acute spinal cord injuries, and 10 without injuries as a control. Findings showed the median urine 3-HPMA concentration was significantly higher in dogs with the injuries compared to the control dogs.

“Urine 3-HPMA is the first assay to indirectly assess acrolein concentration by measuring a metabolite of acrolein in dogs,” Shi says.

The median urinary 3-HPMA concentration in the dogs with acute spinal cord injuries was 5.76 micromoles per gram of creatinine, a compound found in urine, compared to 3.10 micromoles of 3-HPMA per gram of creatinine in control dogs.

While previous research has focused on rats and mice, progressing to dogs takes the research a step closer to research with humans. At the same time, because the dogs suffered their injuries naturally and are much closer to humans in size, they represent a truer comparison to people with spinal cord injuries, Shi says.

Together, these factors increase the likelihood of translating the findings to eventual application to humans, he says.

Ideally, the monitoring approach might be used in personalised medicine to reduce side effects by precisely tailoring drug dosage to individual patients based on the concentration of acrolein.