Dan Wendt has many memories from his 26 years working at 澳门正规博彩十大排行平台, but one day in particular still sticks out in his mind.

2007年的一个早晨，一组研究人员来到澳门正规博彩十大排行平台，展示他们在临床前模型中关于成纤维细胞生长因子受体(FGFR)和c型利钠肽(CNP)信号在调节生长中的相互作用的研究结果.

“The research was very compelling, 澳门正规博彩十大排行平台很快就明白，有证据表明CNP是经济增长的主要监管者,” recalls Dan, Director, CNP Franchise Lead, Musculoskeletal Research at 澳门正规博彩十大排行平台. “澳门正规博彩十大排行平台立即开始了一项专注于生长相关疾病的研究计划，大约一年后，澳门正规博彩十大排行平台对遗传性身材矮小的最常见原因进行了第一次研究, achondroplasia.”

Since that pivotal day in 2007, Dan和澳门正规博彩十大排行平台的研究团队已经取得了重大的科学突破，有助于科学界对生长相关条件的理解. 该公司的方法——使用CNP模拟物来挖掘决定身高的自然过程——已经在10多个临床试验中进行了严格的测试，并将继续在超过3个现实环境中进行评估,100 individuals receiving treatment to date.

“At 澳门正规博彩十大排行平台, 澳门正规博彩十大排行平台遵循科学，将CNP作为澳门正规博彩十大排行平台研究基因生长条件的最佳目标,” says Marcia Kayath, 澳门正规博彩十大排行平台’s Senior Vice President and Head of Global Medical Affairs, who began her career as a physician and endocrinologist. “澳门正规博彩十大排行平台已经在临床研究中严格验证了这种方法，结果大约为4%,500 patient-years of data in clinical trials and real-world usage, 在50多份出版物和演讲中有同行评议的数据，而澳门正规博彩十大排行平台才刚刚开始.”

The Genetics of Human Height

Height is one of the traits most clearly linked to genetics. In studies of thousands of genomes, one signal in particular stood out as a master regulator of height: CNP.

“Quite simply, 这些大规模的基因组研究表明，当CNP过表达时, it can result in tall stature, while loss of CNP signaling can result in short-stature conditions,” explains Chris Bauer, Associate Director, Statistical Genetics at 澳门正规博彩十大排行平台. “这种对身高的双向影响已经在实验室研究中得到证实，这些研究评估了增加或阻断CNP信号的影响.”

早期基因组研究的另一个重要发现是身高和FGFR3基因之间的联系. Using DNA sequencing, 研究人员能够确定FGFR3基因的改变是软骨发育不全的根本原因, the most common form of genetic short stature. 这种基因变化会产生一种改变形式的FGFR3蛋白，这种蛋白会不断发出信号来减缓骨骼生长, resulting in the physical manifestations of skeletal dysplasias, including short stature.

基因研究揭示了另一个重要的见解:CNP和FGFR3水平的变化对身高有着根本不同的影响, CNP信号似乎高度靶向影响骨骼生长.

“CNP信号对身高的影响是双向的，可以微调的, like a dimmer light switch,” says Chris. “While FGFR3 is also involved in bone growth, its effects are more like an on-off switch, which can’t be fine-tuned in the same way.”

这让生物生物学家们想知道，这些见解是否可以用来开发一种更细致入微的方法, adjustable approach that could be evaluated in growth-related conditions.

Navigating Pathways to Find the Ideal Target

当Dan参加2007年关于CNP和FGFR3相互作用的研究报告时, 分子间相互作用的确切机制还不完全清楚.

“FGFR3信号可以激活不同信号通路的真正字母汤, including MAPK/ERK, JAK/STAT, and mTOR/AKT,” he says. “但澳门正规博彩十大排行平台在澳门正规博彩十大排行平台的团队和该领域的其他研究人员最终确定了MAPK/ERK是过度活跃的靶向途径，而这正是CNP发挥作用的途径.”

Unlike FGFR3, CNP signaling can be fine-tuned, 使其成为多种生长相关疾病的有希望的治疗靶点. Contrary to diseases such as cancer, where malignant growth needs to be turned off entirely, growth-related conditions may benefit from a more nuanced approach.

“Based on the clear scientific evidence, we were convinced that if we developed a CNP analog, 它可以从根本上改变澳门正规博彩十大排行平台治疗生长相关疾病的方式,” says Dan. “最棒的是，CNP模拟物利用了人体自身的自然过程之一来影响身高. Plus, this approach bypasses FGFR3, 因此，它可以具有广泛的适用性，而不限于存在FGFR3变化的情况.”

From Scientific Insight to Clinical Reality

澳门正规博彩十大排行平台数十年的科学研究不仅证实了CNP的作用, 但也帮助改变了受生长相关疾病影响的家庭的临床环境.

对CNP的深入了解可能会支持针对几种生长相关疾病的药物开发. 澳门正规博彩十大排行平台继续探索这种方法影响软骨发育不全患者的潜力, 特发性身材矮小(ISS)和多种遗传性身材矮小的条件, including Turner syndrome, SHOX deficiency and Noonan syndrome.

“澳门正规博彩十大排行平台很高兴能够在遗传生长相关疾病的最广泛的临床开发项目中取得进展, 以澳门正规博彩十大排行平台已经获得的大量临床证据为基础,” says Marcia. “Especially for hypochondroplasia and other growth-related conditions, 目前尚无批准的药物可用于治疗潜在病因, 澳门正规博彩十大排行平台正在迅速探索澳门正规博彩十大排行平台的CNP方法如何为家庭提供更好的结果.”