丹·温特（Dan Wendt）在澳门正规博彩十大排行平台工作的26年给他留下了许多回忆, 但有一天，他的脑海中仍然挥之不去.

It was a morning in 2007 when a group of researchers came to 澳门正规博彩十大排行平台 to present their findings from a study on the interaction of fibroblast growth factor receptor (FGFR) and C-type natriuretic peptide (CNP) signaling in regulating growth in preclinical models.

“这项研究非常引人注目, and it quickly became clear to us that there was evidence starting to emerge for CNP as a master regulator of growth-related development,丹回忆道。, 导演, CNP特许经营主管, 澳门正规博彩十大排行平台肌肉骨骼研究. “We immediately began work on a research program focused on skeletal conditions and about a year later had the first derivative of what would become our investigational treatment for the most common cause of genetic short stature, 软骨发育不全.”

从2007年那个关键的日子开始, Dan and 澳门正规博彩十大排行平台’s teams of researchers have led major scientific breakthroughs that have helped contribute to the scientific community’s understanding of skeletal conditions. The company’s approach – using a CNP analog to tap into the natural processes that determine height – has been rigorously tested in more than 10 clinical trials and continues to be evaluated in real-world settings with more than 3,目前已有100人接受治疗.

“在澳门正规博彩十大排行平台, we’ve followed the science with CNP as the optimal target for our research into genetic skeletal conditions,玛西娅·卡亚说, 澳门正规博彩十大排行平台’s Senior Vice President and Head of Global Medical Affairs, 她的职业生涯是从内科医生和内分泌学家开始的. “We’ve rigorously validated this approach in clinical studies — resulting in approximately 4,500个病人年的临床试验和实际使用数据, with peer-reviewed data featured in more than 50 publications and presentations — and we’re just getting started.”

人类身高的遗传学

身高是与基因最明显相关的特征之一. 在对数千个基因组的研究中, one signal in particular stood out as a master regulator of height: CNP.

“很简单, these large-scale genomic studies revealed that when CNP is overexpressed, 它会导致身材高大, 而CNP信号的缺失会导致身材矮小,克里斯·鲍尔解释道。, 副主任, 澳门正规博彩十大排行平台的统计遗传学. “This bidirectional impact on height has been confirmed in laboratory studies that evaluated the effects of either increasing or blocking CNP signaling.”

Another key finding from early genomic studies was the connection between height and the FGFR3 gene. 使用DNA测序, researchers were able to identify alterations in the FGFR3 gene as the root cause of 软骨发育不全, 最常见的遗传性身材矮小. The genetic change produces an altered form of the FGFR3 protein that continuously sends a signal to slow down bone growth, 导致骨骼发育不良的生理表现, 包括身材矮小.

The genetic studies revealed one other crucial insight: changes in CNP and FGFR3 levels have fundamentally different impacts on height, with CNP signaling appearing to be highly targeted to impact skeletal growth.

“The effects of CNP signaling on height are bidirectional and fine-tunable, 就像一个调光开关,克里斯说。. “虽然FGFR3也参与骨骼生长, 它的作用更像是一个开关, 哪一个不能以同样的方式进行微调.”

This led 澳门正规博彩十大排行平台 scientists to wonder if these insights could be leveraged to develop a more nuanced, adjustable approach that could be evaluated in skeletal conditions.

导航路径以找到理想目标

When Dan attended that 2007 research presentation on the interaction between CNP and FGFR3, the exact mechanisms of the molecular interactions were not fully understood.

“FGFR3 signaling can activate a veritable alphabet soup of different signaling pathways, 包括MAPK / ERK, JAK / STAT, 和mTOR / AKT,他说. “But our teams at 澳门正规博彩十大排行平台 and other researchers in the field eventually identified MAPK/ERK as the overactive pathway to target – and this is the pathway where CNP operates.”

不像FGFR3, CNP信号可以微调, making it a promising therapeutic target across multiple skeletal conditions. 与癌症等疾病相反, 哪里的恶性生长需要被完全阻断, 骨骼状况可能受益于更细致的方法.

“基于明确的科学证据, 澳门正规博彩十大排行平台确信，如果澳门正规博彩十大排行平台开发出CNP类似物, it could fundamentally change the trajectory of how we approach therapeutic options for skeletal conditions,丹说. “The great thing is that the CNP analog leverages one of the body’s own natural processes to impact height. +, 这种方法绕过FGFR3, so it could have broad applicability not limited to conditions where changes in FGFR3 are present.”

从科学洞察到临床现实

Decades of scientific research at 澳门正规博彩十大排行平台 not only validated the role of CNP, but also helped change the clinical landscape for families impacted by skeletal conditions.

This deepened understanding of CNP may support the development of medicines for several skeletal conditions. 澳门正规博彩十大排行平台 continues to explore the potential for this approach to impact people living with hypochondroplasia, idiopathic short stature (ISS) and multiple genetic short-stature conditions, 包括特纳综合症, SHOX缺乏症和努南综合症.

“We’re excited to be moving forward with the broadest clinical development program in genetic skeletal conditions, building on the robust body of clinical evidence we’ve already generated,玛西娅说. 特别是对于软骨发育不良和其他骨骼疾病, where there are no currently approved medicines available to treat the underlying causes, we’re moving rapidly to explore how our approach with CNP could provide families with better outcomes.”