Researchers at Georgia State University have successfully revived an ancient gene, dormant for millions of years, potentially offering a significant breakthrough in treating gout and liver diseases. The study, which utilized advanced CRISPR gene-editing technology, demonstrated the ability to lower uric acid levels in human liver cells, a key factor in managing these conditions.
Gout, a painful inflammatory arthritis, results from the accumulation of uric acid crystals in the joints. Elevated uric acid levels are also implicated in various kidney and liver diseases. Humans, unlike most other mammals, lost the functional uricase enzyme, which metabolizes uric acid, between 20 and 29 million years ago. This evolutionary loss may have provided advantages during periods of food scarcity by aiding fat accumulation from fructose metabolism, but it now contributes to prevalent modern diseases.
The research team, led by Professor Eric Gaucher and postdoctoral researcher Lais de Lima Balico, reconstructed an ancestral version of the uricase gene. Introducing this reactivated gene into human liver cells led to a notable reduction in uric acid. Crucially, this intervention also prevented fructose-induced fat accumulation in the liver cells, suggesting a broader therapeutic impact for conditions like fatty liver disease.
This innovative gene therapy approach offers a promising alternative to existing treatments. Current uricase treatments, such as Krystexxa, while effective, can cause significant immune reactions. By enabling the body's own cells to produce the uricase enzyme, this new method could potentially minimize such immune responses. The research, published in Scientific Reports, highlights that while humans lost the functional uricase gene, the cellular machinery to utilize the protein remains intact.
Future research will involve studies in animal models, with the ultimate goal of progressing to human clinical trials. This advancement represents a beacon of hope for millions affected by gout and related liver conditions, potentially offering a more integrated and less reactive therapeutic strategy by restoring a function lost to our ancient ancestors.