MOI-A
Research type
Research Study
Full title
Matrix-directed therapy in older adolescents and adults with osteogenesis imperfecta – the “MOI-A” study
IRAS ID
1006449
Contact name
Nicholas Bishop
Contact email
Sponsor organisation
Sheffield Children’s NHS Foundation Trust
Research summary
Osteogenesis imperfecta (OI) is the commonest inherited cause of bone fragility (approx 1 in 16,000). People with OI suffer bone fragility causing fractures, pain and deformity; sarcopenia causing fatigue and poor endurance; aortic root dilatation and hearing loss. The range of severity is broad with severely affected individuals at risk of early death e.g. from respiratory failure in infancy, or progressively deforming bone disease that leaves them permanently wheelchair bound with scoliosis, basilar invagination and intractable pain. Even the more mildly affected individuals have an increased risk of fracture and suffer with easy fatigability.
Current standard of care
No drug currently has market authorisation to treat OI. Current standard-of-care is multidisciplinary, with pharmacological interventions – primarily bisphosphonates1 - directed at increasing bone mass; however, such interventions are of equivocal efficacy.2 The structural damage that can accumulate as a result of repeated fractures over time may not be reversible. The lack of a treatment with clearly defined efficacy in terms of reducing fracture frequency or the sarcopenia that is increasingly recognised in this condition leads to the consideration of alternatives based on what is known about the molecular pathophysiology of the condition. Existing approaches to the treatment of OI focus on increasing bone mass as a means to address the loss of bone mass, degradation of microarchitecture and the alteration in bone material properties that renders the bone brittle. We suggest that by reducing circulating TGFb levels (see below for supporting evidence) through the use of our intervention, we will both reduce bone turnover and bone loss and have a positive effect on muscle function and quality of life. This is a novel approach that has not been studied previously in a clinical setting.REC name
London - London Bridge Research Ethics Committee
REC reference
23/LO/0158
Date of REC Opinion
11 Aug 2023
REC opinion
Further Information Favourable Opinion