DWORF expression is reduced in a large animal model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease driven by cytosolic calcium overload, which leads to muscle degeneration. Sarco/endoplasmic reticulum calcium ATPase (SERCA), a key regulator of cytosolic calcium levels, exhibits reduced activity in animal models of DMD and human patients. Dwarf open reading frame (DWORF), a positive SERCA regulator, is downregulated in mdx DMD mice, and adeno-associated virus-mediated DWORF overexpression has been shown to ameliorate DMD cardiomyopathy.

Circulatory CCL2 distinguishes Duchenne muscular dystrophy dogs.

To establish a minimally invasive approach to studying body-wide muscle inflammation in the canine Duchenne muscular dystrophy (DMD) model, we evaluated 13 cytokines/chemokines in frozen sera from 90 affected (239 sera) and 73 normal (189 sera) dogs (0.00 to 45.2 months of age).

Adeno-Associated Virus 8 and 9 Myofibre Type/Size Tropism Profiling Reveals Therapeutic Effect of Microdystrophin in Canines.

Background: Adeno-associated virus (AAV) 8 and 9 are in clinical trials for treating neuromuscular diseases such as Duchenne muscular dystrophy (DMD). Muscle consists of myofibres of different types and sizes. However, little is known about the fibre type and fibre size tropism of AAV in large mammals.

SERCA2a overexpression improves muscle function in a canine Duchenne muscular dystrophy model.

Excessive cytosolic calcium accumulation contributes to muscle degeneration in Duchenne muscular dystrophy (DMD). Sarco/endoplasmic reticulum calcium ATPase (SERCA) is a sarcoplasmic reticulum (SR) calcium pump that actively transports calcium from the cytosol into the SR. We previously showed that adeno-associated virus (AAV)-mediated SERCA2a therapy reduced cytosolic calcium overload and improved muscle and heart function in the murine DMD model.