Bone Abstracts

Osteogenesis imperfecta (OI), or brittle bone disease, is a heterogeneous inherited condition and severe forms present already in utero. Persons with severe OI is affected throughout their lifetime with repeated, multiple fractures, short stature and orthopaedic problems, considerable pain and handicap. There is no curative or sufficiently effective symptomatic treatment for OI. Preliminary clinical experience indicates that transplantation of fetal liver derived mesenchymal stem cells (MSC) before and after birth may ameliorate symptoms. The main objective of the international Boost Brittle Bones Before Birth (BOOSTB4) phase I/II multicentre trial is to evaluate the safety and efficacy of pre- and/or postnatal MSC transplantation in severe vital forms of OI (type III and severe type IV). The study will include three groups:

i) Prenatal and postnatal transplantations in circa 15 patients, inclusion during pregnancy

ii) Postnatal transplantation in circa 15 patients, inclusion before one year of age

iii) Historical and prospective controls, at least 30 cases

Over 12 months, the patients will receive four postnatal infusions of same-donor MSC at 4-month intervals. The primary outcome is safety for the fetus, child and pregnant woman. Secondary outcomes relate to efficacy, including fracture frequency, time to fracture, number if fractures at birth, growth, bone mineral density, biochemical bone turnover and clinical OI status. Rapid exome sequencing using a panel targeted for skeletal disorders for definitive molecular diagnosis of OI will be developed. Experience, impact and perception of the therapy will be evaluated in both treatment groups. Non-invasive prenatal diagnosis of OI based on analysis of cell free DNA will be developed. We have established a European network centred around four clinical hubs in Stockholm, Cologne, London and Utrecht/Leiden. Ethical and regulatory applications are underway to conduct this clinical trial. The BOOSTB4 consortium welcomes clinical cases for diagnosis of OI using rapid exome sequencing and for inclusion in the clinical trial. Contact Cecilia Götherström for more information: [email protected] and BOOSTB4.EU

Disclosure: The authors declared no competing interests.