Researchers have identified uric acid as a potential therapy to enhance recovery from acute ischemic stroke using a new method for conducting preclinical animal research. Credit: NIH
Key points:
- Researchers developed a new rigorous system for conducting preclinical research that could result in more successful clinical trials.
- The system leveraged a network of laboratories to develop protocols, procedures, analysis, randomization and blinding that increased scientific rigor and reduced bias.
- The team used their method to test six new stroke treatments and identified uric acid as a promising target requiring further preclinical testing.
A team of researchers from the Keck School of Medicine of USC has developed and tested a new system for performing preclinical research to better translate lab discoveries into effective treatments.
In a new study published in Science Translational Medicine, the team used the system to examine six potential new stroke treatments, identifying the strongest candidate for further study.
“For years, we have tested drugs on animals first, but we often get it wrong,” said lead author Patrick Lyden, MD, professor of physiology and neuroscience and of neurology at USC. “Our primary goal with this research was to show there is a better way to do preclinical testing and that this is one way to get better results that can be replicated.”
For the study, the researchers used animal models that better represent stroke patients. While preclinical research typically relies on young male mice and rats, this time the team included female mice, older mice, mice with diet-induced obesity or hyperglycemia, and rats that were spontaneously hypertensive.
The research team, which spanned six U.S. laboratories dubbed the Stroke Preclinical Assessment Network, employed a novel statistical method to evaluate six potential stroke treatments at four points in the process. Any substances that failed to show sufficient efficacy were immediately dropped from the study.
Only one substance—uric acid—showed efficacy through all four phases of analysis. Although uric acid was a promising treatment based on the primary endpoint, there were no benefits using secondary endpoints, implying that further preclinical animal studies are needed before moving to clinical trials in human stroke patients.
“The study acted as we intended it to by sequentially eliminating the futile drugs until we were left with one,” said Lyden. “We believe uric acid, based on this evaluation, should be studied further.”