Ancient Gene Reactivation May Offer Gout Relief
Long ago, human ancestors lost the ability to utilize a particular gene, but reactivating it might protect against gout, according to a recent experimental study.
Gout, a form of arthritis, leads to intense pain and swelling in the joints. This condition arises when uric acid accumulates in the bloodstream, forming sharp crystals that cause inflammation. Symptoms can appear suddenly and can be quite persistent, lasting days or even weeks.
Although various medications exist to manage high uric acid levels, many have had limited effectiveness or significant drawbacks, including unwanted side effects like adverse immune reactions.
A study released on July 18 in the journal Scientific Reports proposed a novel way to tackle elevated uric acid levels: reviving the function of a gene lost through evolution, using CRISPR gene editing techniques.
“Human cells still recognize what to do with the protein” produced by the lost gene, explained geneticist Eric Gaucher from Georgia State University. Co-author Lais de Lima Balico, a postdoctoral researcher in his lab, contributed significantly to the study.
At this point, the research has mostly been conducted in a lab setting with human cells, but the findings indicate that a gene therapy might eventually become a viable treatment for those suffering from gout.
This condition is relatively common, impacting 1 in 25 individuals globally, yet it is quite rare among mammals aside from primates. Other animals possess an active gene for an enzyme named uricase, which helps break down uric acid, preventing crystal formation. Over time, mutations in humans have rendered this enzyme ineffective in processing uric acid. Some scientists theorize that this adaptation may have helped primates survive cold winters by transforming fruit sugars into fat, allowing them to develop larger brains.
In this recent research, scientists utilized CRISPR to integrate the ancient uricase gene into human liver spheroids, which are 3D cell clusters that mimic real organs. The introduction of the gene led to reduced uric acid levels and less fat accumulation linked to fruit sugar metabolism.
Currently, there are gout treatments utilizing uricase to manage high uric acid levels, like Krystexxa, which contains uricase proteins derived from pig and baboon genes. However, these treatments often trigger intense immune responses and require clinical oversight due to risks like anaphylaxis.
In contrast, a gene therapy that reinstates the original human gene could allow the body to produce uricase naturally. This approach might lower the likelihood of immune reactions, as the uricase protein would be more familiar to the human body.
However, the researchers acknowledge that significant work remains before such therapies can be administered to humans. They aim to transition their studies from liver spheroids to laboratory mice, using nanoparticle systems for direct CRISPR introduction into liver cells.
This gene therapy could potentially revolutionize gout treatment by offering a durable and possibly safer alternative to existing methods. Yet, treatments based on gene editing are still in the early phases of research.
The team hopes that the strategy of repurposing ancient genes for contemporary therapies might have wider applications in the future. “My ultimate goal is to merge molecular evolution with clinical medicine,” Gaucher expressed. “Ideally, we could use ancient proteins or enzymes to create therapies that benefit modern society.”
This article serves as informational content and isn’t intended to provide medical advice.
