Researchers from the Perelman School of Medicine at the University of Pennsylvania recently explored the underlying biological cause and mechanisms behind fibrodysplasia ossificans progressiva (FOP). In the past, researchers from this same team determined that ACVR1 gene mutations caused FOP, a rare genetic disorder which causes bone growth and formation outside of the skeletal structure.

While researchers did explore how this mutation impacted cell changes, little was done to evaluate how the ACVR1 mutation actually affected muscle and muscle repair. In this more recent study, the team noted that dysfunctional muscle repair mechanisms in FOP could be a driver of the condition. To check out the full study findings, take a look at npj Regenerative Medicine. 

Muscle Research

Within this study, the research team utilized mice models of FOP. The research centered around muscle stem cells and fibro-adipogenetic progenitors, two types of muscle tissue stem cells that normally help repair muscle injuries. You see, when muscle is injured, fibro-adipogenetic progenitors expand and recruit muscle stem cells. Once these muscle stem cells join in, they repair and regenerate damaged tissue. As the muscle stem cells mature, fibro-adipogenetic progenitors eventually die off. Through this process, new and stronger muscle fiber is created. 

However, researchers found that this process was dysfunctional in the mice models. Rather than dying off, fibro-adipogenetic progenitors survived longer than expected. This ultimately interrupted the ability of muscle stem cells to do their job, causing smaller and less stable muscle fiber. Ultimately, this allows room for ossification to occur. 

While more research is needed, this suggests that new therapeutic options for FOP could work on both reducing ossification and also finding ways to improve muscle regeneration. 

To read the full source article, head over to SciTechDaily. 

About Fibrodysplasia Ossificans Progressiva (FOP)

As described above, ACVR1 gene mutations commonly cause fibrodysplasia ossificans progressiva (FOP). The gene mutation is inherited in an autosomal dominant pattern, meaning individuals must inherit only one defective gene. Additionally, the ACVR1 gene mutation may occur spontaneously. An estimated 1 in every 1.6 million newborns is born with FOP. 

Altogether, FOP is characterized by heterotopic ossification, or bone formation in areas of the body where bone is not normally present. For example, muscles, tendons, and ligaments may ossify, causing restricted movement. Symptoms become more prevalent in early childhood. Trauma or injuries may also cause painful “flares” of muscle swelling and permanent bone growth. Other symptoms associated with FOP include:

• Loss of mobility
• Chronic inflammation
• Joint stiffness
• Loss of mobility
• Low-grade fever
• Difficulty eating, speaking, or breathing
• Malformed big toe and/or thumbs (present at birth)
• Painful, fibrosis nodules on the neck, back, and shoulders
  • Note: Ossification normally begins around the neck or shoulders before moving to other limbs.