Clinical trials in skeletal dysplasia: a paradigm for treating rare diseases

Background Genetic skeletal dysplasia conditions (GSDs) account for 5% of all birth defects. Until recently, targeted treatments were only available for select few conditions; 1 however, opportunities arising from developments in molecular diagnostic technologies are now leading to unparalleled therapeutic advances. This review explores current GSD clinical trials, their challenges and the hopes for the future. Sources of data A systematic literature search of relevant original articles, reviews and meta-analyses restricted to English was conducted using PubMed up to February 2020 regarding emerging GSD therapies. Areas of agreement We discuss current clinical trials for in achondroplasia, osteopetrosis, osteogenesis imperfecta, hypophosphataemic rickets, hypophosphatasia and fibrous ossificans progressiva. Areas of controversy We explore challenges in GSD drug development from clinician input, cost-effectiveness and evidenced-based practice. Growing points We explore opportunities brought by earlier diagnosis, its treatment impact and the challenges of gene editing. Areas timely for developing research We horizon scan for future clinical trials.