Stakeholder views and attitudes towards prenatal and postnatal transplantation of fetal mesenchymal stem cells to treat Osteogenesis Imperfecta

Abstract

The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial is investigating the safety and efficacy of transplanting fetal derived mesenchymal stromal cells (MSCs) prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI). This study aimed to explore stakeholder views to understand perceived benefits or concerns, identify ethical issues and establish protocols for support and counselling. Semi-structured qualitative interviews were conducted with three groups; 1. Adults affected with OI, with and without children, and parents of children affected with OI; 2. Health professionals who work with patients with OI; 3. Patient advocates from relevant patient support groups. Interviews were digitally recorded, transcribed verbatim and analysed using thematic analysis. Interviews with 56 participants revealed generally positive views towards using fetal MSC transplantation to treat OI. Early treatment was considered advantageous for preventing fractures and reducing severity and could bring psychological benefits for parents. Common concerns were procedure safety, short/long-term side effects and whether transplantation would be effective. Difficulties inherent in decision-making were frequently discussed, as treatment efficacy is unknown and, by necessity, parents will make decisions at a time when they are vulnerable. Support needs may differ where there is a family history of OI compared to an unexpected diagnosis of OI. Explaining fetal MSC transplantation in a way that all parents can understand, clear expectation setting, psychological support and time for reflection during the decision-making process will be crucial to allow parents to make informed decisions about participation in the BOOSTB4 clinical trial.

Current Overview of Osteogenesis Imperfecta

“…Postnatal transplantation with same-donor foetal liver MSCs was performed at 1.6 years of age, and following the procedure, a resumption of vertical growth was observed. Based on these clinical experiences, the first clinical trial of the transplantation of foetal liver MSCs, the Boost Brittle Bones Before Birth (BOOSTB4) trial is ongoing [ 99 , 100 ]. The BOOSTB4 trial is investigating the safety and tolerability of MSC transplantation as a therapy for severe forms of OI (OI type 3 and 4).…”

The role of next‐generation sequencing in the investigation of ultrasound‐identified fetal structural anomalies

“…*Microarray testing would be initiated in tandem with prenatal ES. † Such as prenatal mesenchymal stem cell transplants by in utero transfusion in OI (BOOST4 study) 65 …”

“…† Such as prenatal mesenchymal stem cell transplants by in utero transfusion in OI (BOOST4 study). 65 …”

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

“…Furthermore, MSC transplantation in OI patients has showed promising results leading to increased BMD and decreased fracture risk after transplantation in both mice and humans ( 18 – 21 ). In 2016, EU approved the Boost Brittle Bones Before Birth (BOOSTB4) study whose sole aim is to perform Phase I/II clinical trials on the safety and efficacy of prenatal and/or postnatal transplantation of fetal-derived MSC for severe forms of OI (Type III and IV) ( 22 ). Finally, it has been also shown that allele-specific Col1a1 and Col1a2 silencing using small interfering RNAs leads to reduction of the mutant collagen in both human and mice cell models ( 23 , 24 ).…”