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

Melissa Hill,Catherine Devile,Anna L David,Lyn S Chitty,Cecilia Götherström,Magnus Westgren,Belinda Crowe,Oliver Semler,Celine Lewis,Megan Riddington

doi:10.1038/s41431-019-0387-4

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.

Highlights

Osteogenesis Imperfecta (OI) is a rare metabolic bone disorder that affects ~1 in 20,000 births [1,2,3]
Three participant groups were recruited; (1) Adults affected with OI, with and without children affected with OI, and parents of children affected with OI, who were not affected with OI themselves (“patients and parents”); (2) health professionals; and (3) patient advocates from relevant support groups
Most participants in our study reported feeling positive about stem cell transplantation (SCT) and the BOOSTB4 trial and raised concerns about possible risks and the complexity of decision making

Summary

Introduction

Osteogenesis Imperfecta (OI) is a rare metabolic bone disorder that affects ~1 in 20,000 births [1,2,3]. Common features include bone fragility, osteopenia, short stature, atypical skeletal development, brittle teeth, hearing loss and hypermobile joints [1, 2]. Variants in the COL1A1 and COL1A2 genes that either reduce the amount of collagen or impact on collagen structure are causal in 85–90% of cases [4]. OI has been classified as mild (type 1), moderate (type 4), severe (type 3) or lethal (type 2) [5]. OI is a heterogeneous condition and severity varies widely, including between family members with the same genetic variant [6]. Severe forms can sometimes be identified before birth when ultrasound detects fractures, reduced fetal growth or bowing of the limbs

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