Evaluation of safety and efficacy of multiple intravenous and intraosseous doses of foetal liver-derived mesenchymal stem cells in children with severe osteogenesis imperfecta: the BOOST2B clinical trial protocol

Aims: Current off-label bisphosphonate treatment for osteogenesis imperfecta (OI) does not induce healthy bone formation. Therefore, novel strategies to stimulate osteogenesis and reduce fractures are needed to meet the medical needs of these patients. Preclinical data and case studies show that mu...

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Main Authors: Vrisha Madhuri, Sowmya Ramesh, Annika Goos, Thomas V. Paul, Shyamkumar Nidugala Kesava, Vikram Mathews, Lilian Walther-Jallow, Cecilia Götherström, on behalf of the BOOST2B Study Group
Format: Article
Language:English
Published: The British Editorial Society of Bone & Joint Surgery 2025-03-01
Series:Bone & Joint Open
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Online Access:https://online.boneandjoint.org.uk/doi/epdf/10.1302/2633-1462.63.BJO-2024-0115.R1
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Summary:Aims: Current off-label bisphosphonate treatment for osteogenesis imperfecta (OI) does not induce healthy bone formation. Therefore, novel strategies to stimulate osteogenesis and reduce fractures are needed to meet the medical needs of these patients. Preclinical data and case studies show that multiple intravenous (IV) administrations of mesenchymal stem cells (MSCs) provide promising outcomes in the treatment of OI. In the Boost to Brittle Bones (BOOST2B) trial, we aim to assess the safety and tolerability of multiple IV and intraosseous (IO) administrations of foetal liver-derived MSCs in children aged one to five years diagnosed with severe OI. Methods: A total of 15 children will receive four doses of foetal MSCs IV (3 × 106 cells per kg of body weight) and IO (0.1 × 106 cells per kg of body weight per long bone) at four-month intervals. As a secondary endpoint, the therapeutic effect of the four MSC doses will be assessed based on the annual fracture rate, time to first fracture, bone mineral density, growth, clinical status of OI, and biochemical bone turnover in peripheral blood. Exploratory parameters include quality of life and donor cell engraftment. Conclusion: The BOOST2B trial has been approved by the regulatory agencies in India and is ongoing. It is the first clinical trial designed to evaluate IO administration of MSCs as a potential therapy for OI. Here, we describe the BOOST2B clinical trial protocol. The long-term data on safety and efficacy will be reported once completed. Cite this article: Bone Jt Open 2025;6(3):361–372.
ISSN:2633-1462