Decades of NIH Research Uncover Insights on Rare Bone, Skin, and Endocrine Disease
For many years, doctors have been trying to understand why patients with fibrous dysplasia/McCune-Albright Syndrome experience such unique symptoms. This rare genetic disease can cause patients to break their bones easily, experience early puberty, and even lose their vision and hearing in some cases. Thanks to 26 years of research at the National Institutes of Health (NIH), more effective treatments are now available for this complex condition.
What is fibrous dysplasia/McCune-Albright Syndrome?
Fibrous dysplasia (FD) and McCune-Albright Syndrome (MAS) are two distinct conditions that share a common genetic variation. When both conditions occur together, it is known as FD/MAS. FD primarily affects the bones, while MAS impacts the skin and endocrine system responsible for regulating hormones in the body.
FD/MAS is a genetic disease that develops during fetal development and is not inherited. Early signs of FD/MAS include large birthmarks and premature puberty. The symptoms can range from mild to severe, including chronic pain, bone deformities, and a high rate of bone turnover. In some cases, bone lesions can grow and put pressure on organs and nerves, leading to vision, hearing, or breathing problems. Additionally, FD/MAS can cause hormonal imbalances such as hyperthyroidism.
Treatments for FD/MAS include surgical interventions, hormone therapy, and medical device implants to manage the symptoms and improve the quality of life for patients.
Unlocking the source of FD/MAS
While FD/MAS was first documented in medical literature in 1937, the underlying cause remained a mystery until 1991. Dr. Allen Spiegel and his team at the National Institute of Diabetes and Digestive and Kidney Diseases identified a specific protein mutation responsible for the skin and hormonal manifestations of FD/MAS. Further research by Dr. Pamela Robey at the National Institute of Dental and Craniofacial Research revealed that the same mutation affects bone lesions in patients with FD/MAS.
Tracking FD/MAS over the lifespan
In 1998, a natural history study was initiated to understand how FD/MAS progresses throughout a person’s life. Dr. Robey and Dr. Michael Collins enrolled over 300 patients ranging from 1 to 102 years old in the study to monitor their symptoms, bone health, and treatment responses. This comprehensive approach led to the development of personalized treatment plans based on each patient’s unique symptoms.
Recent discoveries and ongoing research
One significant finding from the study was the overproduction of a protein called RANKL in FD cells, leading to increased bone turnover and the formation of new lesions. Researchers explored the use of a RANKL blocker, denosumab, to reduce bone turnover and prevent new lesions in animal studies and clinical trials.
While there are approved medications for managing hormonal symptoms of FD/MAS, preventing the growth of bone lesions remains a challenge. Current research led by Dr. Alison Boyce is investigating the use of denosumab to halt the formation of bone lesions in children with FD/MAS. Additionally, another study is examining the effects of a drug called burosumab on blood phosphate levels in patients with FD/MAS, as these individuals often have low phosphate levels crucial for bone health.
In conclusion, the dedicated research efforts at the NIH have shed light on the complexities of FD/MAS and paved the way for more targeted treatments and improved quality of life for patients. Ongoing studies continue to explore new therapeutic options and advance our understanding of this rare disease.