The Boost Brittle Bones Before Birth (BOOSTB4) project is focused on the shared ambition of a group of leading European clinicians, researchers and industrial stakeholders to translate fetal mesenchymal stem cell (MSC) transplantation into the clinic as a therapy for severe Osteogenesis Imperfecta (OI).
What is the problem being addressed?
OI is a debilitating inherited disorder with prenatal onset leading to osteopenia (low bone density), bone brittleness, short stature and chronic pain. Affected children and adults suffer from multiple fractures, requiring hospitalisation and surgery, and often leading to irreversible deformities. Current therapies are only partly effective at treating the disease, and pre-clinical and initial clinical data show that MSCs could be used to treat OI. The BOOSTB4 project therefore aims to develop fetal MSC transplantation as a therapy for OI.
Why is it important for society?
Individuals with OI suffer from life-long repeat fractures, pain, disability and reduced quality of life. There is no cure for OI and almost no treatment options exist, therefore the implications of a successful therapy for these individuals are vast. Persons with OI are affected throughout their lifetime; the costs of managing the disease and caring for patients, borne by healthcare providers and society, are extremely high. Typically, care for these patients requires a large multidisciplinary team. The care includes direct medical costs, direct non-medical costs, and indirect costs/production loss associated with OI.
Successful clinical demonstration of MSC therapy in OI will pave the way for the treatment of many inherited diseases where no or few therapy options are available, especially for children. Decreasing the severity of such congenital diseases will result in life-long benefits for the affected individuals and their families from birth onwards, as well as reducing the above mentioned costs.
What are the overall objectives?
The overall objective of BOOSTB4 is to develop a treatment using MSCs for severe types of OI. The main core of the BOOSTB4 project is the open label phase I/II trial that evaluates the safety and efficacy of postnatal (n=15) or pre- and postnatal (n=5) administration of multiple doses of first trimester human allogeneic fetal liver MSCs as a treatment of severe OI type III/IV. The primary endpoint of the trial is safety and tolerability of intravenous administration of MSCs to the infant, fetus and pregnant woman. Efficacy is evaluated as secondary endpoints and includes fracture frequency, time to fracture, number of fractures at birth, growth, bone mineral density and biochemical bone turnover in blood. Paracrine effects, influence on recipient immune cells, donor cell engraftment and Quality of Life are evaluated as exploratory endpoints. Ethical standards and risks, experience, impact and perception of the therapy, non-invasive prenatal diagnosis and health economics are also investigated in the project.
Conclusions of the action
The BOOSTB4 consortium has successfully developed a promising therapy for OI. This includes a method for non-invasive prenatal diagnosis of OI, a biosignature of fetal MSCs and response after therapy, manufacturing of MSCs for clinical use, and investigation of the safety of pre-and/or postnatal intravenous administration of fetal MSCs to young children with OI. To date, after 70 doses of same-donor MSCs, no significant short-term complications have been recorded.
