New Understanding of Muscle-Repair Cells May Lead to Treatments for Neurological Diseases

Researchers found that fibro-adipogenic progenitors activate the IL-6-STAT3 signaling pathway, leading to muscle wasting.

The pharmaceutical industry has been challenged to discover treatments for neurological disorders such as ALS amyotrophic lateral sclerosis (ALS) despite significant investments in R&D efforts. As research into the mechanism of ALS and other brain diseases progresses, pharma companies continue to search for effective treatments. Recent examples include Biogen’s $535 million deal with AliveGen to develop drugs for muscle-wasting disorders that block myostatin and the startup Aquinnah Pharmaceuticals’ development of treatments for neurodegenerative diseases that target stress granules that form in response to injury.

More information has been discovered by researchers at Sanford Burnham Prebys Medical Discovery Institut. They recently reported that muscle-repair cells called fibro-adipogenic progenitors (FAPs) activate the IL-6-STAT3 signaling pathway, which causes the immune system to be over-active, resulting in muscle wasting. Importantly, when this signaling pathway was blocked, the muscle wasting was halted.

The team studied different participants in muscle repair, including stem cells and macrophages (immune cells that clean up debris). They observed that once a muscle is injured, macrophages appear, followed by FAPs and then stem cells. The FAPs are gone if the healing process progresses normally, usually within a week.

In muscles where loss of neurons, or denervation, has occurred, however, the FAPs remain and are present in high numbers, and high levels of IL-6, an inflammatory protein that promotes muscle atrophy, exist, while macrophages and stem cells are not detected.

The research team will next work to better characterize the IL-6-STAT3 pathway and the unusual FAPs that are involved in it so as to enable the development of drugs that can inhibit its functioning. "Now that we have found a key difference in these FAP cells, we have an opportunity to selectively remove the bad, disease-causing cells or convert the cells so they can repair nerves. We can start working on designing medicines that target these cells or possibly use them as markers of disease progression, which can't come soon enough for patients and their caregivers,"” said Pier Lorenzo Puri, head of the research team

Nigel Walker

Mr. Walker is the founder and managing director of That’s Nice LLC, a research-driven marketing agency with 20 years dedicated to life sciences. Nigel harnesses the strategic capabilities of Nice Insight, the research arm of That’s Nice, to help companies communicate science-based visions to grow their businesses. Mr. Walker earned a bachelor’s degree in graphic design with honors from London College of Communication, University of the Arts London, England.