Introduction: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by heterotopic ossification, congenital skeletal abnormalities especially of the great toes, and several features of accelerated aging. Missense mutations in the in the gene for ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor are responsible for all known cases of FOP. Progression of the condition is relentless and occurs clinically via episodic inflammatory exacerbations or flare-ups and/or spontaneously (without flare-ups).

Areas covered: The current pharmacological targets, potential designs for clinical trials, and possible treatment approaches using experimental and repurposed agents for FOP are reviewed [PubMed 2000–2019, using FOP as a key search term].

Expert opinion: The growing number of pharmacological interventions for FOP includes blocking the activity of the mutant FOP receptor, quenching inflammatory triggers, inhibiting connective tissue progenitor cells that give rise to ectopic endochondral ossification, and minimizing the micro-environmental factors that promote lesion progression. In light of the rarity of FOP, new approaches to clinical trial design, including delayed start and n = 1 designs, are considered. Finally, a schema for pharmacological management of FOP in anticipation of approved medications and the availability of repurposed drugs is proposed.

简介：骨化性纤维增生症（FOP）是一种超罕见的遗传病，其特征是异位骨化，先天性骨骼异常（尤其是大脚趾的骨骼异常）以及加速衰老的一些特征。ACVR1 / ALK2编码激活素A受体I /激活素样激酶2（骨形态发生蛋白（BMP）I型受体）的基因中的错义突变是造成所有已知FOP病例的原因。病情恶化是无情的，并且在临床上会通过发作性炎症加重或发作而和/或自发地发生（没有发作）。

涵盖领域：综述了目前的药理学目标，临床试验的潜在设计以及使用实验性药物和重新定型的FOP药物可能的治疗方法[PubMed 2000–2019，使用FOP作为关键搜索词]。

专家意见：越来越多的FOP药物干预措施包括阻断FOP突变体的活性，猝灭炎症触发因素，抑制结缔组织祖细胞引起的异位软骨内骨化以及最小化促进病变进展的微环境因素。鉴于FOP的稀缺性，考虑了新的临床试验设计方法，包括延迟启动和n = 1设计。最后，提出了一种用于FOP药理管理的方案，以期批准已批准的药物和重新使用的药物。