Scientists have successfully revived a gene that has been dormant in humans for over 20 million years, with the potential to treat gout and related health issues. The gene, known as uricase, produces an enzyme that reduces levels of uric acid in the blood, which can lead to painful conditions like gout and other serious health problems, including kidney disease and hypertension.
When there is an excess of uric acid, it can crystallize in the joints and kidneys, a condition termed hyperuricemia. According to researchers Lais Balico and Eric Gaucher from Georgia State University, the absence of uricase has left humans vulnerable to these health risks. “We wanted to see what would happen if we reactivated the broken gene,” Gaucher stated.
Research Insights and Methodology
The team explored the evolutionary history of uricase, noting that human ancestors lost the gene due to evolutionary pressures approximately 20 to 29 million years ago. During that time, higher levels of uric acid were advantageous for converting fruit sugars into fat, aiding survival during food shortages. In modern society, where food scarcity is less of an issue, the high uric acid levels are now more harmful than beneficial.
Utilizing the CRISPR gene-editing technique, Balico and Gaucher reconstructed an ancient version of the uricase gene based on functional versions still found in other mammals. The researchers tested their findings on engineered human liver cells, where the revived gene successfully produced uricase, leading to reduced levels of uric acid and associated fatty deposits.
“This had the desired effect, lowering uric acid and stopping the cells from turning excess fructose into triglycerides — the fats that build up in the liver,” Gaucher explained. Positive results were also observed in more complex 3D liver spheroids, indicating that the uricase enzyme was effectively targeting the correct cellular compartments.
Future Implications and Health Concerns
The implications of reactivating the uricase gene extend beyond gout. High levels of uric acid have been linked to various cardiovascular diseases and conditions like kidney stones. “Hyperuricemia is a dangerous condition,” Gaucher emphasized. “By lowering uric acid, we could potentially prevent multiple diseases at once.”
While the research shows promise, further studies are essential to ensure that reactivating the uricase gene can be done safely in humans, without disrupting other critical biological processes. Approximately 20% of people in the United States are believed to have hyperuricemia, a condition that can also be influenced by dietary choices, such as the consumption of red meat and alcohol.
Existing treatments for gout do not work for everyone and may come with undesirable side effects. “Our genome-editing approach could allow patients to live gout-free lives and potentially prevent fatty liver disease,” Gaucher concluded.
The findings from this groundbreaking research have been published in Scientific Reports, marking a significant step forward in the fight against gout and related health issues. As the research progresses, the team hopes to explore further applications of this ancient gene revival in human health.
