Scientists discovered how a rare genetic disease called X-linked hypophosphatemia (XLH) damages muscle cells. The disease causes a protein called FGF23 to build up in the body, which weakens bones and causes skeletal problems. In this study, researchers grew human muscle cells in the lab and exposed them to FGF23 to see what happens. They found that FGF23 interferes with the genes that help muscles grow and develop, even though it doesn’t stop muscle cells from multiplying. This discovery helps explain why people with XLH experience muscle weakness and pain, and could lead to better treatments in the future.

The Quick Take

  • What they studied: How a protein called FGF23 affects human muscle cells grown in a laboratory dish
  • Who participated: Muscle cells from three healthy volunteers were grown in the lab and tested with different amounts of FGF23 protein
  • Key finding: FGF23 significantly reduced the activity of genes needed for muscles to grow and develop properly, suggesting this protein directly damages muscle function in people with XLH
  • What it means for you: This research helps scientists understand why people with X-linked hypophosphatemia experience muscle weakness. While this is early-stage lab research and doesn’t immediately change treatment, it opens the door to developing new therapies that could block FGF23’s harmful effects on muscles.

The Research Details

Researchers took muscle tissue samples from three healthy volunteers and grew muscle cells in laboratory dishes. They then exposed these cells to FGF23 protein at three different concentrations (similar to low, medium, and high levels found in patients). They measured what happened to the cells after 24 and 48 hours of exposure, looking at whether cells multiplied and whether important muscle-building genes were turned on or off.

This type of study is called an ‘in vitro’ study, which means it happens in a test tube or dish rather than in a living person. Scientists use these studies to understand how specific proteins affect cells at a detailed level before testing in animals or humans.

Understanding exactly how FGF23 damages muscle cells is crucial for developing new treatments. By studying cells in a controlled lab environment, researchers can identify the specific molecular switches that FGF23 turns off, which could become targets for future medicines. This foundational knowledge is necessary before doctors can design therapies to protect muscles in XLH patients.

This is a preliminary laboratory study with a small sample size (three volunteers), so results need confirmation in larger studies. The findings are based on cells grown in dishes, which don’t perfectly replicate what happens in a living body. However, the study was carefully designed with proper controls and measured multiple important muscle genes, making the results scientifically sound for this type of research.

What the Results Show

When muscle cells were exposed to FGF23, the protein did not stop cells from multiplying or dividing normally. This was an important negative finding because it showed that FGF23’s harmful effects on muscles aren’t about preventing cell growth.

However, FGF23 dramatically reduced the activity of genes that control muscle development and function. Specifically, four key genes (Myf-5, MyoD-1, Myogenin, and MRF4) that act like ‘master switches’ for muscle growth were significantly turned down. These genes are essential for converting muscle cells into mature, functioning muscle fibers.

The protein also reduced genes for irisin (a hormone that helps muscles work properly), myosin heavy chain (a protein that makes muscles contract), and desmin (a structural protein that holds muscle cells together). Additionally, FGF23 reduced the genes for its own receptors and a helper protein called KLOTHO, suggesting the cells were trying to protect themselves from FGF23’s effects.

The study found that FGF23 also affected myostatin, a protein that normally limits muscle growth. The reduction in myostatin might seem beneficial, but in the context of reduced muscle-building genes, it indicates that FGF23 is disrupting the entire system that controls muscle development. The reduction in FGF23 receptors and KLOTHO suggests that muscle cells may attempt to defend themselves by reducing their ability to receive FGF23 signals, though this defense appears incomplete.

While XLH is known to cause muscle weakness and pain in patients, very few studies have directly examined how FGF23 affects muscle cells. Most previous research focused on FGF23’s effects on bones and phosphate metabolism. This study fills an important gap by showing that FGF23 directly interferes with muscle development at the cellular level, supporting patient observations of muscle problems and suggesting these aren’t just secondary effects of bone disease.

The study used muscle cells from only three healthy volunteers, so results may not apply to everyone. The cells were grown in artificial laboratory conditions that don’t perfectly replicate the complex environment inside a living body. The study tested FGF23 in isolation, but in real patients, many other factors also affect muscle. Additionally, this research doesn’t show whether blocking FGF23 would actually improve muscle function in patients with XLH—that would require further studies.

The Bottom Line

This is fundamental research that helps explain muscle problems in XLH but doesn’t yet lead to specific patient recommendations. Current XLH treatment focuses on managing phosphate and calcium levels. This research suggests that future treatments might also need to address FGF23’s direct effects on muscles. If you have XLH, continue following your doctor’s current treatment plan while staying informed about emerging therapies. (Confidence: Low—this is early-stage research)

This research is most relevant to people with X-linked hypophosphatemia and their families, as well as doctors treating XLH. It’s also important for pharmaceutical companies developing new XLH treatments. General readers should understand that this explains why XLH causes muscle problems, even though it doesn’t immediately change treatment options.

This is basic laboratory research, so practical benefits are likely years away. Typically, discoveries like this take 5-10 years to develop into actual treatments that doctors can prescribe. The next steps would be testing in animal models, then eventually clinical trials in human patients.

Want to Apply This Research?

  • For XLH patients: Track muscle strength and fatigue weekly using a simple scale (1-10) and note activities that cause pain or weakness. Record this alongside your current phosphate and calcium management to help your doctor see patterns.
  • If you have XLH, work with your healthcare team to develop a gentle, consistent exercise routine. While this research doesn’t change current treatment, maintaining muscle activity may help preserve strength. Log your exercise type, duration, and how you felt afterward to identify what works best for your body.
  • Create a long-term log of muscle-related symptoms (weakness, pain, fatigue) and correlate with your treatment adherence and FGF23 levels (if monitored). This personal data will be valuable as new treatments emerge and can help your doctor assess whether future therapies targeting FGF23 are working.

This article describes early-stage laboratory research and should not be used to diagnose, treat, or manage X-linked hypophosphatemia or any other medical condition. The findings are from cells grown in dishes and have not been tested in humans. If you or a family member has XLH or experiences unexplained muscle weakness, consult with a qualified healthcare provider or genetic specialist. Current treatment recommendations for XLH should continue as prescribed by your doctor. This research may eventually inform future treatment options, but such developments require additional studies and clinical trials.