A study recently published in Molecular Biomedicine identified obestatin, a hormone produced by the stomach, as a potential add-on therapy for patients with Duchenne muscular dystrophy (DMD) due to its ability to restore cellular function and reduce muscle damage in DMD mouse and cell models.
“This finding represents a substantial advance in our understanding of the complex process of skeletal muscle remodeling under dystrophic conditions,” the authors wrote. “It also identifies a potential candidate for combined therapeutic approaches, allowing an improvement of muscle stability and function that will increase the efficiency of gene and cell therapies.”
The researchers found that as DMD mice age, the function of their mitochondria — the cell organelle responsible for producing energy — declines. When they injected the mice with obestatin, however, they observed substantial improvements in mitochondrial function.
Treated mice also displayed an improved ability to break down and recycle waste, which is essential for maintaining cellular health. These findings were confirmed in a human cell-based model of DMD.
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Additionally, obestatin treatment led to muscle fiber restructuring and reduced creatine kinase levels in DMD mice.
What is creatine kinase?
Creatine kinase (CK) is an enzyme found in muscles. When muscles become damaged, CK leaks out of the muscles and into the bloodstream. In diagnosing DMD, CK levels are checked in a blood sample and if they are unusually high, this is a key indicator of DMD.
Further investigation revealed that obestatin activates protein phosphatase 3 (PPP3), a molecule that regulates skeletal muscle function and possibly mitochondrial capacity. The study showed that PPP3 activated other genes that support muscle health.
Many of the genetic and cellular therapies that exist today for DMD aim to repair specific mutations, the authors explained. Therefore, they remain limited by their ability to only target one or a few mutations at a time. The extent to which therapies that correct mutations also improve existing muscle damage is unknown, too.
“Therefore, obestatin offers unique opportunities for muscle regenerative medicine, either as a single therapy or in combination with others,” the researchers concluded.
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