New research by the RVC finds promising treatment for sclerosteosis patients
New research from the Royal Veterinary College (RVC) has identified porcupine inhibition – a strategy that blocks a key bone-related signalling pathway (Wnt) – as a promising pharmacological treatment for severe sclerosteosis.
Sclerosteosis is an ultrarare neglected genetic disease, affecting approximately 100 people in the world. The disease is characterised by progressive skeletal overgrowth and other symptoms, such as the absence of nails and fused fingers. Those impacted also experience recurrent acute facial nerve palsy, with facial distortion often also arising in early childhood. Sclerosteosis patients also exhibit early-life hearing loss, life-threatening intracranial pressure through skull bone thickening, and jugular vein compression.
Due to limited previous research, no pharmacological therapies exist meaning this potentially fatal disease can currently only be treated by high-risk surgical procedures.
Conducting this research, the RVC team, in collaboration with biopharmaceutical company UCB, used in vitro techniques with bone cells and in vivo approaches with mice to explore whether a specific porcupine inhibitor (LGK974) was a potential sclerosteosis therapeutic. Key findings included that:
- LGK974 significantly reduced osteoblast (the main bone-building cell) bone forming activity, defined through analysis of several in vitro endpoints.
- In vivo research, conducted in young mice with a genetic alteration mimicking sclerosteosis and with their skeleton stimulated as a young child’s would, revealed significant reductions in bone mass across the skeleton.
- LGK974 treatment reduced skull and ear bone mass of mice with sclerosteosis disease, indicating that porcupine inhibition may effectively limit skeletal overgrowth at sites with severe/fatal pathology.
- Disease modification across the skeleton in this model indicated that LGK974 therapy would likely also be an option for treating disease early in children, potentially avoiding high-risk surgical treatments in these patients.
Dr Scott Roberts, Reader in Translational Skeletal Research and senior author of the study, said:
“Sclerosteosis is an ultrarare disease and due to this is often neglected for further research, despite contributing greatly to our understanding of bone biology. As such, I am excited that a research partnership with UCB has discovered a new therapeutic approach for this potentially fatal disease through analysis of the most severe pathologies in a preclinical mouse model. The next stage is to generate a complete pharmacology dataset in preparation for translation to human studies.”
Dr Gill Holdsworth, Director, Skeletal Remodelling Group, and co-author of the study, at UCB, said:
“We are proud to contribute our expertise to this collaborative effort with the Royal Veterinary College, which reflects the shared dedication to unlocking innovative solutions for individuals with severe disease. This study not only advances our understanding of bone biology but also lays the groundwork for potential new treatments.”
Notes to Editors
Reference
Dreyer, T.J., Keen, J.A.C., Wells, L.M. et al. Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies. Bone Res 13, 44 (2025). https://doi.org/10.1038/s41413-025-00406-3
The full paper can be accessed at: https://www.nature.com/articles/s41413-025-00406-3
For media enquiries, please contact:
- Jasmin De Vivo at jasmin.devivo@plmr.co.uk or rvc@plmr.co.uk
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About the RVC
- The Royal Veterinary College (RVC) is the UK's largest and longest established independent veterinary school and is a Member Institution of the University of London.
- It is one of the few veterinary schools in the world that hold accreditations from the RCVS in the UK (with associated recognition from the AVBC for Australasia, the VCI for Ireland and the SAVC for South Africa), the EAEVE in the EU, and the AVMA in the USA and Canada.
- The RVC is ranked as the top veterinary school in the world in the QS World University Rankings by subject, 2024.
- The RVC offers undergraduate and postgraduate programmes in veterinary medicine, veterinary nursing and biological sciences.
- The RVC is a research-led institution, with 88% of its research rated as internationally excellent or world class in the Research Excellence Framework 2021.
- The RVC provides animal owners and the veterinary profession with access to expert veterinary care and advice through its teaching hospitals and first opinion practices in London and Hertfordshire.