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People Involved

Bronwen Williams

Kathryn Date

Kerri Morris

Gethin Owen

Mr John Turgoose

Mr John Turgoose
Information Systems Manager - Hull Health Trials Unit

Project Description

Osteogenesis imperfecta (OI) causes skeletal fragility, bone pain, sarcopenia and reduced connective tissue resilience, shown as hypermobility and aortic root dilatation (in adults). There is no effective treatment for OI. Current agents only target skeletal tissue. Bisphosphonates (anti-resorptive) have reduced fracture frequency in mildly affected children; benefits are equivocal in severe cases. Adults have had no clear benefit of either anti-resorptive or anabolic therapy, e.g. PTH. Preclinical studies in severely affected OI mice show increased TGFβ signalling and increased bone turnover; anti-TGFβ antibody reduces bone resorption (by ~25%) and restores skeletal architecture. Inhibition of the TGFβ signalling pathway in other preclinical models where TGFβ signalling is increased (Marfan's, Duchenne Muscular Dystrophy) show improved skeletal and cardiac muscle outcomes. Inhibition of this pathway thus has the potential to improve both bone and muscle outcomes. We propose a novel approach, repurposing an existing drug (losartan) that reduces circulating TGFβ and is licensed for use in children and adults, to target both muscle and bone using a Bayesian approach to define an optimal biologic dose in 50 adults with OI aged 18-65. Additional efficacy outcomes - grip strength, bone microarchitecture by high resolution peripheral quantitative CT and OI-specific quality of life - will provide the basis for an application for Orphan Drug Designation and health economic evaluation.

Type of Project Project
Project Acronym REMEDI4ALL
Status Project Live
Funder(s) Innovate UK
Value £922,056.00
Project Dates Sep 1, 2022 - Aug 31, 2027

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