ATLANTA – Scientists are investigating a novel gene therapy approach to treat gout, a common and painful condition characterized by the accumulation of uric acid crystals in the joints. The research, led by geneticist Eric Gaucher at Georgia State University, focuses on restoring a lost gene function that breaks down uric acid.

The study, with postdoctoral scholar Lais de Lima Barica as the second co-author, has so far been conducted in lab studies using human cells. The initial results suggest that gene therapy could become a viable treatment option for gout patients in the future.

gout affects approximately 1 in 25 people globally, but it is notably rare in mammals othre then primates. Most animals possess an active gene for uricase, an enzyme that efficiently breaks down uric acid, preventing crystal formation. Humans, though, have accumulated mutations that render their uricase enzyme ineffective. Some scientists propose that this loss of function may have been beneficial, as increased uric acid levels can convert fruit sugar into fat, perhaps aiding primate survival during periods of scarcity and supporting brain development.

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Previous research has successfully identified ancient genes responsible for uricase production through ancestral gene inference. This process involves analyzing the DNA of modern species, constructing evolutionary trees, and estimating the genetic sequences of ancient organisms.By recreating these ancient proteins in the lab, researchers hope to unlock new therapeutic possibilities.

In the current study, the research team employed CRISPR gene editing to insert the ancient uricase gene into human liver spheroids,which are three-dimensional tissue models that mimic the function of full-sized organs.The introduction of the ancient gene led to a reduction in uric acid levels and a decrease in fat accumulation related to fruit sugar metabolism.

Existing gout treatments utilize uricase to manage uric acid levels. Such as, Krystexxa involves injections of uricase proteins derived from pig and baboon gene sequences. however, these protein-based therapies often trigger strong immune responses and necessitate careful clinical monitoring due to the risk of anaphylaxis.

Potential Benefits of Gene therapy

A gene therapy approach that restores the original human gene sequence could enable the body’s own cells to produce uricase, potentially minimizing immune reactions because the uricase protein sequence would be largely recognized by the body.

“My ultimate goal is to be able to wed molecular evolution and clinical medicine,”

The researchers are now moving from liver spheroids to lab mice, utilizing nanoparticle delivery systems to introduce CRISPR gene-editing components directly into liver cells.

This gene therapy has the potential to revolutionize gout treatment by offering a long-lasting and potentially safer alternative to current therapies. However, gene-editing therapies are still in the early stages of development.

The researchers hope that adapting ancient genes for modern therapies could be more broadly applied in the future.

“my ultimate goal is to be able to wed molecular evolution and clinical medicine,” Gaucher said.”Ideally we can use ancient proteins or ancient enzymes to develop therapeutics to help modern society.”