Osteogenesis Imperfecta Phenotype-based Assays
Research type
Research Study
Full title
Osteogenesis Imperfecta: Phenotype based assays on cultured osteoblasts and fibroblasts
IRAS ID
220463
Contact name
Meena Balasubramanian
Contact email
Sponsor organisation
Sheffield Children's NHS Foundation Trust
Duration of Study in the UK
3 years, 0 months, 4 days
Research summary
Osteogenesis Imperfecta, often referred to as Brittle Bone Disease is the most common form of inherited bone fragility. In Sheffield, we have the largest cohort of children with Osteogenesis Imperfecta (OI) within Western Europe. Next generation sequencing: the new technology now available to us means that the genetic origins of many diseases are becoming clearer, and this is impacting on the development of new treatments. For example, studying a rare childhood bone disease (Osteoporosis-Pseudoglioma syndrome) underpinned the development of two new osteoporosis treatments (Denosumab and Anti-sclerostin antibodies).
Through a study funded last year by The Children’s Hospital Charity, we have identified candidate genes of interest in bone fragility patients with unknown causality. However, the mechanism behind how some of these candidate genes cause bone fragility is not entirely clear. Work is ongoing to understand the mechanism and pathways involved in bone biology through collaboration with colleagues at the University of Sheffield.
Following on from understanding critical pathways in bone biology and establishing the role these candidate genes play, we need to next, explore therapeutic targets and how disease-causing mechanisms can be reversed first at the cellular level. To this effect, we have a commitment from Genzyme Rare Bone Disease Research to undertake phenotype-based assays on cells obtained from patients with fragile bones and compare this with ‘normal, healthy’ children. This will help us understand what exactly happens in these patients and how this can be reversed by small molecules which can be used to develop target treatments in future.
This study would improve outcomes for patients with this rare disease and cement our position as research leaders in this field of medicine.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
17/YH/0026
Date of REC Opinion
24 Feb 2017
REC opinion
Further Information Favourable Opinion