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

Jansen 's干骺端软骨发育不良（JMC）是一种罕见的骨骼发育和矿物质离子平衡疾病。JMC是由甲状旁腺激素（PTH）受体突变引起的，这种受体在生长板、骨骼和肾脏中含量特别高。JMC的PTH受体突变过度活跃，导致骨骼畸形、极度矮小和慢性肾脏疾病，往往需要在晚年进行透析或肾移植治疗。其他并发症包括颅骨间隙过早闭合，导致脑神经损伤和潜在的视力和听力丧失。目前尚无有效的治疗方法。主要合作者已经确定了一种肽（称为PTH- ia），可以降低突变PTH受体的高基线活性。该项目的目标是完成必要的临床前研究，以使PTH-IA用于JMC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.