INFORM October 2025

8 • inform October 2025, Vol. 36 (9)

One dose of

Despite affecting high numbers of American adults—more than 30 million according to the CDC— osteoarthritis (OA) has limited treatment options and no cure. OA is the most common form of arthritis, marked by discomfort, stiffness, and swelling in affected joints, frequently the knees, hips, hands, and spine. It is a painful, debilitating, progressive condition. If you are diagnosed with OA today, providers may recommend physical therapy, pain relieving medication, crutches, a cane, or joint replacement surgery, but they cannot offer a cure (https://tinyurl.com/492356). therapy eases osteoarthritis in mice Kelly Carroll Fat-1 gene

Farshid Guilak, professor of orthopedic surgery at Washington University in St. Louis, Missouri, is trying to change that. “It is one of the few diseases where we have absolutely nothing we can do to affect the disease process,” he said. Guilak and six colleagues recently published a study showing that gene therapy targeting a fatty acid desaturase successfully reduced the severity of OA in mice (https://doi.org/10.1073/pnas.2402954121). Gene therapy is a treatment that corrects a malfunctioning gene to prevent, or help the body resist, disease. Other research teams have developed sim ilar treatments for other diseases, including sickle cell, hemophilia A, and beta-thalassemia. The number of available therapies is growing rapidly. TRANSFORMING FAT Here researchers placed five-week-old mice on either a high-fat diet rich in omega-6 fatty acids or a regular diet. About four weeks later, the mice were given a single dose of fat-1 gene therapy, administered by an ade no-associated virus (AAV). Matlock Jeffries, director of the Oklahoma Medical Research Foundation’s Arthritis Research Center, said that this type of viral-me diated gene therapy does not change the host organism’s genome. It expresses the therapeutic gene over a long period, requiring infrequent administration. While AAV-administered gene therapies are not perma nent, they last a long time, Jeffries said, estimating that gene expression would gradually decrease after one to two years.

• Osteoarthritis is a common and painful condition of the joints with no available cure. • A single dose of fat-1 gene therapy systemically converts omega-6 fatty acids into omega-3 fatty acids and reduces the severity of injury- and age-related OA in experimental mouse models. • More experiments are needed to clarify how fat-1 gene therapy may translate to humans.