St. Louis, MO (October 14, 2024) According to the Centers for Disease Control, nearly 20% of children and teens are considered obese. Research shows it can have a dramatic impact on a variety of health conditions, including arthritis, heart conditions and other metabolic problems, and the American Academy of Pediatrics now recommends early and intensive treatment to combat obesity. Over the last four years, Shriners Children's St. Louis researchers have been working to develop a new way to prevent the effects of childhood obesity.
Using gene therapy, Shriners Children's St. Louis Director of Research Dr. Farshid Guilak and Senior Scientist Dr. Ruhang Tang have discovered a revolutionary new way to convert harmful fatty acids into beneficial ones, making it possible for children battling obesity to lower the risk of other health problems, particularly arthritis.
"We've learned that the number one preventable risk factor for arthritis in children is being overweight," said Dr. Guilak. "Our typical response is simply telling kids to lose weight, without addressing the larger issue. Childhood obesity has become an epidemic, and as a result, arthritis is becoming increasingly common in children. One of our key findings is that it's not just the obesity itself that's harmful, but also the diet. The types of fatty acids children consume play a significant role in a child's weight gain. And once children are obese, it opens the door for other significant health problems that can be hard to reverse."
Dr. Tang said their gene therapy technique involves utilizing an inactive virus, adeno-associated virus (AAV), to deliver the gene for a specific enzyme into cells. The new gene therapy automatically converts highly inflammatory Omega-6 fatty acids to Omega-3 fatty acids, which are better for the body's metabolic health. Dr. Guilak said Omega-6 acids, which come from fatty foods and vegetable oil such as in fried foods, tend to promote inflammation and can lead to health issues such as arthritis, heart disease, and metabolic problems. Omega-3s, as found in fish and certain nuts, can support a healthier metabolic profile by improving insulin sensitivity, promoting fat metabolism, and reducing inflammation and the risk of obesity-related diseases. Dr. Natalia Harasymowicz, co-lead of the study, said that their gene therapy was also able to lower the number of pro-inflammatory cells that are crucial in promoting obesity-related inflammation and arthritis.
In this study, the researchers studied a type of arthritis that is very common in children, termed "post-traumatic arthritis", caused by injury to the knee such as a tear in the meniscus tissue that serves as a stabilizer and cushion in the knee. The team found that one injection of the gene therapy significantly decreased the effects of a high-fat, omega-6-rich diet on overall metabolic health and knee arthritis. Of particular interest was the finding that diet-induced obesity led to premature "aging" in these mice, which was prevented by gene therapy.
"What we are observing is that obesity results in old knees in young patients", said Dr. Guilak. "The modern diet, especially in the United States, tends to be high in Omega-6s and low in Omega-3s, which can lead to an imbalance, especially for kids. The gene therapy we developed will automatically convert omega-6 to omega-3 fatty acids in your body, effectively turning bad fats into good fats. Arthritis can be a very painful and debilitating condition for children so we're hopeful that this research will help reduce the risk of it developing and make treatments more effective. The implications for how this research might be used in the future are vast but we're excited about the potential for it to help kids lead healthier lives."
Dr. Guilak is also the Mildred B. Simon Professor of Orthopaedic Surgery at Washington University in St. Louis and co-Director of the Washington University Center of Regenerative Medicine. His team is working with the Food and Drug Administration (FDA) to head into clinical trials in the next 3-5 years.
This research was supported by Shriners Children's and the National Institutes of Health.
Ruhang Tang, Natalia S. Harasymowicz, Chia-Lung Wu, Yun-Rak Choi, Kristin Lenz, Sara J. Oswald, Farshid Guilak. Gene therapy for fat-1 prevents obesity-induced metabolic dysfunction, cellular senescence, and osteoarthritis. Proceedings of the National Academy of Sciences USA, [date] 2024.
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