New research conducted by the Royal Veterinary College (RVC) has shed light on a promising pharmacological treatment for severe sclerosteosis. This rare genetic disease affects approximately 100 individuals worldwide and is characterized by progressive skeletal overgrowth, absence of nails, fused fingers, recurrent acute facial nerve palsy, early-life hearing loss, and other life-threatening symptoms.
The study, published in the journal “Bone Research,” explored the use of porcupine inhibition as a therapeutic strategy for sclerosteosis. Porcupine inhibition involves blocking a key bone-related signaling pathway known as Wnt. The researchers collaborated with biopharmaceutical company UCB to investigate the potential of a specific porcupine inhibitor, LGK974, in treating the disease.
Key findings from the research include:
– LGK974 significantly reduced bone-forming activity in osteoblasts, the main bone-building cells, as observed through various in vitro endpoints.
– In vivo studies using young mice with a genetic alteration mimicking sclerosteosis showed significant reductions in bone mass across the skeleton following LGK974 treatment.
– LGK974 treatment led to decreased skull and ear bone mass in mice with sclerosteosis, indicating the potential for limiting skeletal overgrowth at sites with severe pathology.
– The study suggested that LGK974 therapy could modify disease progression across the skeleton, offering a possible alternative to high-risk surgical procedures in affected individuals.
Dr. Scott Roberts, the senior author of the study, expressed excitement about the discovery of a new therapeutic approach for sclerosteosis. He emphasized the importance of further research to translate these findings into potential treatments for patients. Dr. Gill Holdsworth, a co-author from UCB, highlighted the collaborative effort and dedication to developing innovative solutions for individuals with severe bone diseases.
The research contributes to advancing our understanding of bone biology and lays the groundwork for future studies aimed at developing new treatments for sclerosteosis. The next steps involve generating a comprehensive pharmacology dataset to pave the way for human clinical trials.
For more information, the study titled “Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies” can be accessed in the journal “Bone Research” (DOI: 10.1038/s41413-025-00406-3). The Royal Veterinary College and UCB are committed to exploring novel therapeutic options for rare diseases like sclerosteosis.
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