PREPARATION OF AN INVESTIGATIONAL NEW DRUG (IND) APPLICATION WITH FOOD AND DRUG ADMINISTRATION (FDA) FOR A TREATMENT FOR JANSEN'S METAPHYSEAL CHONDRODYSPLASIA

詹森干骺端软骨发育不良（JMC）是一种骨骼发育和矿物质离子平衡的超罕见疾病。JMC是由甲状旁腺激素（PTH）受体突变引起的，该受体在生长板，骨骼和肾脏中的水平特别高。JMC的突变型PTH受体过度活跃，导致骨畸形、身材矮小和慢性肾病，这些疾病通常需要在以后的生活中通过透析或肾移植进行治疗。其他并发症包括颅骨之间的空间过早闭合，导致颅神经受损，并可能导致视力和听力损失。目前，没有有效的治疗JMC。主要合作者已经确定了一种肽（称为PTH-IA），可以降低突变型PTH受体的高基线活性。本项目的目标是完成必要的临床前研究，以使JMC的PTH-IA的临床试验。

Jansen’s metaphyseal chondrodysplasia (JMC) is an ultra-rare disease of skeletal development and mineral ion balance. JMC is caused by mutations in the parathyroid hormone (PTH) receptor, which is present at particularly high levels in growth plates, bones and kidneys. The mutant PTH receptors of JMC are overactive, resulting in bone deformities, extremely short stature and chronic kidney disease, which often requires treatment by dialysis or kidney transplantation later in life. Other complications include premature closure of the spaces between the bones of the skull, leading to damage of cranial nerves and potential vision and hearing loss. Currently, there is no effective treatment for JMC. The lead collaborators have identified a peptide (termed PTH-IA) that can reduce the high baseline activity of the mutant PTH receptors. The goal of this project is to complete the preclinical studies necessary to enable clinical trials of the PTH-IA for JMC.