An important modulator of the immune system, a gene called DC40, may determine the severity of Duchenne muscular dystrophy (DMD), according to a study published in The American Journal of Human Genetics.
This finding suggests that drugs targeting CD40 may improve symptoms of DMD.
“This research opens new therapeutic avenues to try to develop therapies for DMD,” Eric Hoffman, professor of pharmaceutical sciences at the School of Pharmacy and Pharmaceutical Sciences at Binghamton University in New York, and senior author of the study, said in a press release.
Hoffman and colleagues analyzed the genes of more than 100 DMD patients and found that the CD40 gene exhibited polymorphism among the patients, meaning that there were subtle differences in the gene. The differences led to slight differences in the immune system, which affected the severity of DMD.
“The immune system needs to be balanced: too much or too little is a bad thing in any immune response. This balance may be shifted in muscular dystrophy due to the CD40 polymorphism,” Hoffman said.
All DMD patients have mutations in the dystrophin gene that causes the inability to produce dystrophin in the muscles. The disease primarily affects boys. The severity of the condition may differ greatly among patients with some boys losing the ability to walk as young as age 8, while others may be able to walk into their 20s.
Scientists believe that the actions of other genes, called modifier genes, may play an important role in modulating the severity of the DMD.
The CD40 gene activates special immune cells called antigen presenting cells. The role of the antigen presenting cells is to recognize and capture foreign bodies that enter the human body. That action leads to a broad variety of immune and inflammatory responses.
Although it is not fully understood how differences in the CD40 gene modulate the severity of DMD, the authors speculate that certain forms of the CD40 protein may reduce signaling efficiency between cells, which might lead to regeneration failure and fibrosis in the muscles of DMD patients.