Tolvaptan

Scientists have successfully grown 'mini kidneys' in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease. Scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully grown 'mini kidneys' in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease. 'Mini kidneys,' or kidney organoids, are kidney-like structures grown in the lab using stem cells. In the study led by NTU's Lee Kong Chian School of Medicine (LKCMedicine), researchers grew the organoids using skin cells derived from patients with polycystic kidney disease (PKD), a prevalent form of genetic condition that affects 1 in 1000 individuals across all ethnicities.* People with PKD often progress to end-stage kidney disease between their 50s and 60s, with the standard treatment options available being dialysis or a kidney transplant. However, dialysis significantly compromises a patient's quality of life, while a transplanted kidney can be challenging to acquire. One other option is the Food and Drug Administration (FDA) approved drug Tolvaptan, which is very costly and has severe side effects on the liver. To address the need for more effective treatment for PKD patients, the NTU research team sought to better understand the disease by engrafting their newly developed mini kidneys into mice. Previous studies were conducted on mini kidneys grown in a dish, which could only partly mimic the kidney structure and function. The NTU scientists engrafted the mini kidneys into live mice to comprehensively replicate the pathological features of kidney disease, including blood flow, fluid movement (tubular fluid) and cellular communication with other organs. Lead investigator Assistant Professor Xia Yun at LKCMedicine said, "Engrafting the kidney organoid in mice provided us with a physiologically sophisticated approach to studying polycystic kidney disease as we were able to successfully emulate critical disease characteristics similar to those observed in human kidney patients." Critical disease characteristics included abnormalities like the spontaneous formation of cysts in the kidneys and the subsequent damage to its tiny tubes. In their study, reported in the scientific journal Cell Stem Cell, the NTU research team said that they believed their engrafted mini kidneys were high quality because cysts sustained without extra stress stimulation or chemicals, even after they were removed from the live mice for further investigations in a dish. In contrast, previous kidney organoids grown in a dish cannot form cysts without stress stimulation. Co-investigator Assistant Professor Foo Jia Nee at LKCMedicine said, "The similarity between the disease manifestation observed in our engrafted mini kidney model and the real-life experiences of polycystic kidney disease patients suggest that growing kidney organoids and engrafting them into live mice could be beneficial in studying the disease and a useful tool to test new treatments." Metabolic defects in polycystic kidney disease Scientists have long known that abnormalities in a structure on kidney cells, or the primary cilium, cause cysts to form in kidneys. However, tests to understand the regulatory mechanism and relationship between the primary cilium and cell metabolism (autophagy) in live mice with PKD, have not been possible until now. By studying the development of PKD in live mice and testing cellular pathways, researchers found evidence that boosting autophagy could reduce the severity of cysts in the mini kidney. After establishing that boosting autophagy could reduce cysts, the NTU scientists shortlisted 22 drugs known for their effects on cell metabolism and tested them in the lab. Results showed that minoxidil, a clinical drug widely used to cure hypertension and hair loss, effectively reduced cyst formation in the novel mouse model. Asst Prof Xia Yun said, "Our study has demonstrated how cysts in polycystic diseased kidneys can be reduced by boosting autophagy, suggesting that this could be a promising treatment for PKD. Moreover, the proven clinical safety of minoxidil may allow it to be quickly re-purposed to treat PKD patients in clinic. However, more research will be needed to establish this potential." Commenting as an independent expert, Associate Professor Ng Kar Hui, Senior Consultant, Division of Paediatric Nephrology, Dialysis and Renal Transplantation, Department of Paediatrics, Khoo Teck Puat -- National University Children's Medical Institute, National University Hospital, said, "Polycystic kidney disease is one of the biggest causes of chronic kidney diseases among adults. An effective treatment may potentially ameliorate the rising numbers of people with kidney failure in Singapore. The establishment of such models in live organisms brings us one step closer to finding more treatment options. In future studies, the NTU team will test the efficacy of minoxidil and adapt the mini kidney models to investigate other burgeoning kidney diseases without a strong genetic underpinning, such as diabetic kidney disease. * Harris, P.C., and Torres, V.E. (2009). Polycystic kidney disease. Annual Review of Medicine. Volume 60, 321-337.

编者按：本文来自新康界，作者慧玲；赛柏蓝授权转载，编辑相宜高血压药是历次国家带量采购的重点对象，随着集采落地执行，相继有三十多个品种被纳入集采，但大部分高血压药在集采后销售额明显“缩水”。如今第十批带量采购近在眼前，哪些高血压药品种有望纳入新一批国采？01昔日“药王”退居四线，同比下降60.1%数据显示，2023年高血压药在等级医院销售额约达242亿元。在2023高血压化药TOP10产品中，昔日“药王”硝苯地平跌落，销售额大幅下滑为13.96亿元，从第一的宝座退居第四，同比下降60.1%。2023全国等级医院高血压药化药销售额TOP10排名第二的美托洛尔较去年相比，销售额也下滑明显，仅17.75亿元，同比下降39.7%；此外还有非洛地平、缬沙坦氨氯地平也分别下滑17.7%、25.8%。不过销售额实现正向增长的品种仍占大多数，如沙库巴曲缬沙坦钠、艾司洛尔、阿利沙坦酯、贝尼地平等，分别增长70.6%、18.3%、15.5%和31.5%。其中，沙库巴曲缬沙坦钠以36.5亿元的销售额反超硝苯地平和美托洛尔，从第三爬升至第一的宝座。沙库巴曲缬沙坦钠原研来自诺华，于2017年进入中国市场（商品名：诺欣妥），用于治疗心衰，后被纳入2020年国家医保目录，2021年6月，在中国率先获批用于原发性高血压治疗。2021年，院内销售额一举突破20亿元，同比增长170%。目前尚无国产沙库巴曲缬沙坦钠产品上市，首仿药席位仍在空缺，但关于该药的上市注册申请并不少，在审评审批中的药企覆盖超20家。其中，上海宣泰海门药业为首家新分类报产的企业，也不乏科伦药业、倍特药业、正大天晴、齐鲁制药、石药集团等明星药企申报，竞争格外激烈。02这7大品种有望纳入第十批集采在高血压药的细分赛道中，排在市场份额首位的作用于肾素-血管紧张素系统的药物销售额约109亿元，截至目前，该子分类下已有十余个品种进入带量采购范围。排名第二的钙通道阻滞剂(CCB)达86.43亿元，该子分类头部通用名均已纳入集采，且均为仿制药中标。作用于肾素-血管紧张素系统的药品全国等级医院销售情况在高血压用药中排名第三的β-受体拮抗剂约46亿元，随着美托洛尔等药物在第七批集采中标，β-受体拮抗剂在零售渠道保持正增长，而在院内表现为负增长。高血压作为患病率最高的慢性药，在历届集采中向来是“重头戏”，集采所涉及的品种范围不断扩大，剂型更加丰富，在2023年7月执行的第八批集采中有5个品种入选，在第九批集采中也有4个品种被纳入目录。除去已纳入国家集采的品种，目前高血压化药还有7个品种满足集采门槛，符合申报资格企业数达5家及以上，共有5个口服常释剂型、1个注射剂、1个缓释控释剂型，包括沙库巴曲缬沙坦钠、艾司洛尔、多沙唑嗪、螺内酯、托伐普坦、替米沙坦氢氯噻嗪和马昔腾坦。从品种过评情况看，20个高血压化药（以药品名称计）过评企业数（以企业名计）达10家及以上，其中苯磺酸氨氯地平、卡托普利、缬沙坦氨氯地平、吲达帕胺、硝苯地平控释均达20家及以上。从企业过评情况看（以集团计），目前94个高血压化药（80个通用名药品）已有企业过评，涉及超200家药企。华海药业领跑，过评品种数达16个；上海医药以15个品种紧接其后；华润医药以14个品种排位第三；扬子江药业以12个品种排位第四；浙江诺得药业以11个品种排位第五。从厂家销售格局看，诺华、辉瑞、阿斯利康等跨国药企领跑，齐鲁制药、信立泰等国内药企排名靠前，其中诺华、南京海辰药业、桂林南药等企业销售额增速均超过20%。END内容沟通：13810174402医药代表交流群扫描下方二维码加入银发经济市场机遇交流群扫描下方二维码加入左下角「关注账号」，右下角「在看」，防止失联