Micro-dystrophin gene therapy could greatly extend survival and improve heart and muscle function in Duchenne muscular dystrophy (DMD), but it may also lead to heart inflammation that patients and families should know about, according to research published recently in JACC: Basic to Translational Science.
Researchers tested this therapy in mice with a severe form of DMD that more closely mimics human disease. Treated mice lived well past 52 weeks; in comparison, untreated mice usually died around nine weeks of age. This result shows that micro-dystrophin gene therapy holds promise for increasing life expectancy for patients with DMD.
Beyond survival, treated mice showed better heart function. Heart measurements such as ejection fraction and fractional shortening improved to levels similar to healthy mice. Viral delivery of micro-dystrophin boosted dystrophin levels in the heart muscle, which is normally lacking in DMD.
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In addition, important features like left ventricular diameters were restored to normal ranges. These results mean that for people with DMD, such treatment could help prevent heart failure and maintain better heart pumping ability over time should this research eventually be translated into use in humans.
However, this study also found reasons for caution. The treated mice developed a thicker heart septum, the wall dividing the heart chambers, due to inflammation. This was confirmed by examining the tissue, which showed immune cell infiltration and signs of increased collagen production.
Although overall heart function stayed normal, these changes suggest that inflammation could cause long-term problems or complicate treatment. For patients, this means doctors would need to monitor the heart carefully after gene therapy.
“Our study shows for the first time that micro-dystrophin gene replacement therapy in the dKO model can be associated with long-term cardiac alterations, and opens up perspectives for understanding the consequences of using this approach in DMD patients,” the study’s authors said.
Researchers also examined muscle health throughout the body. Treated mice had improved skeletal muscle weight gain and muscle structure closer to healthy controls, with fewer signs of degeneration. However, they also found signs of muscle damage such as increased creatine kinase, and muscle fibers showed some signs of ongoing stress.
Altogether, this research supports micro-dystrophin gene therapy as a promising option for people with DMD. Still, it also shows that patients will need careful, long-term monitoring to manage possible inflammation and heart changes that might come with the therapy.
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