更新于：2024-11-01

Hypoparathyroidism

甲状旁腺功能减退症

更新于：2024-11-01

基本信息

别名

Decreased parathyroid hormone secretion、Deficiency of PTH、Deficiency of parathyrin

+ [35]

简介

A condition caused by a deficiency of PARATHYROID HORMONE (or PTH). It is characterized by HYPOCALCEMIA and hyperphosphatemia. Hypocalcemia leads to TETANY. The acquired form is due to removal or injuries to the PARATHYROID GLANDS. The congenital form is due to mutations of genes, such as TBX1; (see DIGEORGE SYNDROME); CASR encoding CALCIUM-SENSING RECEPTOR; or PTH encoding parathyroid hormone.

关联

项与甲状旁腺功能减退症相关的药物

Palopegteriparatide

帕罗培特立帕肽

靶点

CaSR x PTH1R

作用机制

CaSR拮抗剂 [+2]

在研机构

Ascendis Pharma A/S [+3]

原研机构

Ascendis Pharma A/S

在研适应症

甲状旁腺功能减退症

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2023-11-17

Allogeneic processed Thymus Tissue

靶点-

作用机制

组织替代物

在研机构

Sumitomo Pharma Co., Ltd. [+1]

原研机构

Enzyvant Therapeutics GmbH初创企业

在研适应症

胸腺发育不全

非在研适应症

迪格奥尔格综合征

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2021-10-08

Pamiparib

帕米帕利

靶点

PARP1 x PARP2

作用机制

PARP1抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2021-04-30

235

项与甲状旁腺功能减退症相关的临床试验

NCT05114980 / RecruitingN/AIIT

Parathyroid Allotransplantation in Medically Refractory Hypoparathyroidism

Options for treatment of severe, refractory hypocalcemia are limited for the thousands of patients in the United States who suffer from hypoparathyroidism. Parathyroid allotransplantation is an emerging treatment that provides hope for these individuals. Currently, this therapy has only been successfully provided by a few centers in the world. In the UAB PATH trial, we propose to become one of the few centers worldwide to successfully achieve parathyroid allotransplantation in transplant-naïve patients.

开始日期2025-07-01

申办/合作机构

The University of Alabama at Birmingham

NCT06645899 / Not yet recruitingN/AIIT

Creation, Management and Analysis of a National Database of Patients Affected by Hypoparathyroidism or Pseudohypoparathyroidism

The goal of this observational study is to create, manage and analyze a multicenter national database of patients affected by hypoparathyroidism or pseudohypoparathyroidism, aimed at collecting and studying anamnestic, diagnostic, genetic, clinical, and therapeutic data in a relatively wide number of patients with these two rare pathologies, in Italy.
The study will include 41 specialist clinical centers of endocrinology, pediatric endocrinology, pediatrics, and endocrine surgery, located throughout the Italian territory, and to which patients refer from all the 20 regions of Italy.
Data will be collected over time, both in retrospective and prospective manners, during the 10-year duration of the study, starting from the recruiting visit (basal visit) and then during each follow-up visits patients will undergo for the control of disease at the recruiting clinical centers.
Collected data will include both the most classic traits of the pathology and the less common ones, with the final goal of refining and deepening medical knowledge in the field of these two clinical conditions affecting parathyroid function and calcium homeostasis, and, thus, to be able to define optimal clinical and therapeutic management of patients, improving their quality of life.
The main aspects this observational study aims to assess and clarify are:
1. Evaluation of prevalence and incidence of hypoparathyroidism, globally and in its different etiological forms, and of pseudohypoparathyroidism in Italy.
2. Clinical characterization of different etiological forms of hypoparathyroidism, through both cross-sectional and longitudinal analyses of collected data.
3. Clinical characterization of pseudohypoparathyroidism, through both cross-sectional and longitudinal analyses of collected data.
4. Over time collection of data on bone status and bone fragility in patients with hypoparathyroidism and pseudohypoparathyroidism, to evaluate the prevalence and incidence of fragility fractures in these patients, globally and also based on gender, age, and disease etiology.
5. Over time evaluation of response to pharmacological therapies in patients with hypoparathyroidism and pseudohypoparathyroidism The study will include two independent cohorts of female and male patients of any age, one including patients with chronic hypoparathyroidism of each etiological forms (cohort 1), and one including patients with pseudohypoparathyroidism (cohort 2). The study does not include either any control group/comparison group or healthy volunteers.
The study itself does not involve any medical intervention or drug administration. Pharmacological treatments for which data on response to therapy will be collected in the database, are those administered to patients for the control/treatment of hypoparathyroidism or pseudohypoparathyroidism, regardless of their inclusion in this observational study.

开始日期2024-11-04

申办/合作机构-

NCT06531941 / Not yet recruiting临床2期

An Extension Study to Evaluate the Long-Term Safety and Tolerability of MBX 2109 in Patients With Hypoparathyroidism Who Completed the 12-Week Treatment Period in the Phase 2 Study, MBX-2H1002 Study (Avail-Ext)

The purpose of this study is to evaluate the long-term safety and tolerability of MBX 2109 in patients with hypoparathyroidism who completed the 12-week treatment period in the Phase 2 study, MBX-2H1002.

开始日期2024-10-01

申办/合作机构

MBX Biosciences, Inc.初创企业

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100 项与甲状旁腺功能减退症相关的转化医学

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0 项与甲状旁腺功能减退症相关的专利（医药）

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13,919

项与甲状旁腺功能减退症相关的文献（医药）

2025-01-01·Bone

Predictors of lumbar spine trabecular bone score in women with postsurgical hypoparathyroidism

Article

作者: Amato, Angélica Amorim ; Sobrinho, Alaor Barra ; Freire, Daniel Humberto Dias ; Carvalho, Ana Rachel Teixeira Batista

Hypoparathyroidism is a rare disease that markedly reduces bone remodeling, leading to increased bone mineral density and changes in bone microarchitecture. However, it is currently unclear how these changes affect fracture risk. In this study, we investigated bone mass by dual-energy x-ray absorptiometry, the occurrence of morphometric vertebral fractures, and bone microarchitecture by assessing trabecular bone score in women with postsurgical hypoparathyroidism. We included 67 women with hypoparathyroidism aged 52.9 ± 12.3 years and 63 age (52.9 ± 12.3 years) and body mass index-matched controls, which were assessed for femoral and lumbar spine bone mineral density, trabecular bone score, and vertebral fractures by dual-energy x-ray absorptiometry. Women with hypoparathyroidism had significantly higher bone mineral density at the lumbar spine, femoral neck, and total hip compared with controls despite similar trabecular bone score values. Vertebral fracture assessment indicated that two women with hypothyroidism presented vertebral fractures, both aged over 65 years. Conversely, no vertebral fractures were detected in control women. In a multivariate linear regression model, we found that older age, diabetes, and lower lumbar spine mineral density were significant predictors of lower trabecular bone score values. Our findings indicate that vertebral fractures are not common among women with postsurgical hypoparathyroidism aged under 65 years. Moreover, trabecular bone score values were similar in women with hypoparathyroidism and age-matched controls and were associated with traditional risk factors for fractures, such as older age, type 2 diabetes, and lower spine bone mineral density. LAY SUMMARY: Chronic parathyroid hormone deficiency decreases bone turnover and modifies skeletal properties, although the impact of these changes on fracture risk remains unclear. We studied 67 women with postsurgical hypoparathyroidism and 63 age and body mass index-matched healthy controls and found that bone mineral density is increased in women with hypoparathyroidism despite similar trabecular bone score values and a low occurrence of morphometric vertebral fractures. This suggests that the low bone turnover in hypoparathyroidism increases bone mass, but this is not accompanied by improved bone microarchitecture, indicating that trabecular bone score may be a valuable tool to complement the assessment of skeletal health and the risk of fractures in this condition.

2025-01-01·Methods in Molecular Biology

Monitoring Calcium-Sensing Receptor (CaSR)-Induced Intracellular Calcium Flux Using an Indo-1 Flow Cytometry Assay

Article

作者: Gorvin, Caroline M ; Howles, Sarah A. ; Howles, Sarah A ; Gorvin, Caroline M.

The calcium-sensing receptor (CaSR) has a critical role in maintaining serum calcium concentrations within the normal physiological range, and mutations in the receptor, or components of its signaling and trafficking pathway, cause disorders of calcium homeostasis. Inactivating mutations cause neonatal severe hyperparathyroidism or familial hypocalciuric hypercalcemia (FHH), while gain-of-function mutations cause autosomal dominant hypocalcemia (ADH). Characterizing the functional impact of mutations of the CaSR, and components of the CaSR-signaling pathway, is clinically important to enable correct diagnoses of FHH and ADH, optimize management, and prevent inappropriate parathyroidectomy or vitamin D supplementation. CaSR signals predominantly by activating the G-alpha subunit-11 to mobilize calcium release from intracellular stores. Thus, measurement of CaSR-induced intracellular calcium (Ca²⁺_i) signaling is the gold standard method to investigate the pathogenicity of CaSR genetic variants. This protocol describes a method to assess CaSR-induced Ca²⁺_I signaling using the Indo-1 calcium indicator dye and flow cytometry. This method has been used to assess multiple genetic variants in CaSR and components of its signaling and trafficking pathway in HEK293 cells.

2024-12-31·Animal Cells and Systems

HSPA5 and FGFR1 genes in the mesenchymal subtype of glioblastoma can improve a treatment efficacy

Article

作者: Lee, Ju Young ; Park, Jongkeun ; Hong, Dongwan

Tyrosine kinase inhibitors (TKIs) have emerged as a potential treatment strategy for glioblastoma multiforme (GBM). However, their efficacy is limited by various drug resistance mechanisms. To devise more effective treatments for GBM, genetic characteristics must be considered in addition to pre-existing treatments. We performed an integrative analysis with heterogeneous GBM datasets of genomic, transcriptomic, and proteomic data from DepMap, TCGA and CPTAC. We found that poor prognosis was induced by co-upregulation of heat shock protein family A member 5 (HSPA5) and fibroblast growth factor receptor 1 (FGFR1). Co-up regulation of these two genes could regulate the PI3K/AKT pathway. GBM cell lines with co-upregulation of these two genes showed higher drug sensitivity to PI3K inhibitors. In the mesenchymal subtype, the co-upregulation of FGFR1 and HSPA5 resulted in the most malignant subtype of GBM. Furthermore, we found this newly discovered subtype was correlated with homologous recombination deficiency (HRD) In conclusion, we discovered novel druggable candidates within the group exhibiting co-upregulation of these two genes in GBM, suggest potential strategies for combination therapy.

634

项与甲状旁腺功能减退症相关的新闻（医药）

2024-10-28

·GlobeNewswire-Health Care

MBX Biosciences to Participate in Upcoming November Investor Conferences

CARMEL, Ind., Oct. 28, 2024 (GLOBE NEWSWIRE) -- MBX Biosciences, Inc. (NASDAQ: MBX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel precision peptide therapies for the treatment of endocrine and metabolic disorders, today announced that its management team will participate in the following upcoming investor conferences: Guggenheim Inaugural Healthcare Innovation Conference Date: Tuesday, November 12, 2024Format: Fireside chatTime: 3:30 p.m. ESTLocation: Boston, MA Stifel 2024 Healthcare Conference Date: Monday, November 18, 2024Format: Fireside chatTime: 3:00 p.m. ESTLocation: New York, NY Jefferies London Healthcare Conference Date: Wednesday, November 20, 2024Format: Company presentationTime: 3:30 p.m. GMTLocation: London, UK Live webcasts can be accessed on the investors section of the MBX Biosciences website at https://investors.mbxbio.com/news-events/events. Access to the webcast replay will be available approximately two hours after the completion of the event and will be archived on the Company’s website for approximately 90 days. About MBX BiosciencesMBX Biosciences is a biopharmaceutical company focused on the discovery and development of novel precision peptide therapies based on its proprietary PEP™ platform, for the treatment of endocrine and metabolic disorders. The Company is advancing a pipeline of novel candidates for endocrine and metabolic disorders with clinically validated targets, established endpoints for regulatory approval, significant unmet medical needs and large potential market opportunities. The Company’s pipeline includes its lead product candidate MBX 2109, in Phase 2 development for the treatment of chronic hypoparathyroidism (HP); MBX 1416, in Phase 1 development for the treatment of post-bariatric hypoglycemia (PBH); and an obesity portfolio that includes MBX 4291, as well as multiple discovery and pre-clinical candidates in development for the treatment of obesity. The Company is based in Carmel, Indiana. To learn more, please visit the Company website at www.mbxbio.com and follow it on LinkedIn. About MBX’s Proprietary Precision Endocrine Peptide (PEP™) Platform MBX was founded by global leaders with a transformative approach to peptide drug design and development. Leveraging this expertise, the Company designed its proprietary Precision Endocrine Peptide™ (PEP™) platform to overcome the key limitations of unmodified and modified peptide therapies and to improve clinical outcomes and simplify disease management for patients. PEPs are selectively engineered to have optimized pharmaceutical properties, including extended time-action profiles and consistent drug concentrations with low peak-to-trough concentration ratios, consistent exposure to target tissues, and less frequent dosing. Media Contact:Kate BurdickInizio Evoke Commskate.burdick@inizioevoke.com 860-462-1569 Investor Contact:Jim DeNikeMBX Biosciencesjdenike@mbxbio.com

临床2期临床1期

2024-10-28

·创鉴汇

16家创新药公司获融资！小分子靶向药新锐登陆纳斯达克 | 一周融资

▎药明康德内容团队编辑据创鉴汇不完全统计，上周（10月21日至10月27日）全球大健康领域共披露融资事件35起，总额超100亿元。按照金额划分，亿元及以上融资15起。按照已披露的融资轮次划分，早期融资（B轮以前）16起，中后期融资（B轮及以后）13起。生物医药领域共16家公司获融资，涉及药物类型包括小分子靶向药物、放射性药物、细胞疗法等。 #01 Septerna登陆纳斯达克关键词：小分子靶向药物最新融资：IPO 10月25日，Septerna在纳斯达克上市，总收益约为2.88亿美元。Septerna致力于开发靶向G蛋白偶联受体（GPCR）的小分子药物，其中SEP-786是一种治疗甲状旁腺功能减退症的口服小分子PTH1R激动剂，目前正在进行一项1期临床试验；SEP-631是一种选择性口服小分子MRGPRX2负变构调节剂（NAM），最初用于治疗慢性荨麻疹，MRGPRX2在肥大细胞活化和脱颗粒中发挥着重要作用。抑制MRGPRX2的口服疗法可以选择性地抑制肥大细胞，并具有联合治疗的潜力。 #02 Seaport Therapeutics完成2.25亿美元B轮融资关键词：精神病药物最新融资：2.25亿美元B轮本轮投资机构：ARCH Venture Partners、CPP Investments、Foresite Capital、Goldman Sachs Alternatives等 10月21日，Seaport Therapeutics今日宣布完成了超额认购的2.25亿美元B轮融资。公司将利用这笔资金推进其临床阶段的创新药物管线，并进一步提升Glyph技术平台的能力。Glyph是Seaport的专有技术平台，利用淋巴系统来增强药物的口服给药能力。通过Glyph平台，药物如同膳食脂肪一样通过肠道淋巴系统吸收并运输到血液循环中。旨在提高药物的口服生物利用度，避免首过效应，并减少肝酶升高、肝毒性和其他副作用，从而推动那些因这些限制而受阻的临床活性药物。其管线中进展最快的候选药物是SPT-300，一种口服孕烷醇酮的前药，正在2b期临床试验中用于治疗伴或不伴焦虑困扰的抑郁症。 #03 Alpha-9 Oncology完成1.75亿美元C轮融资关键词：癌症放射性药物最新融资：1.75亿美元C轮本轮投资机构：Abrdn、Ascenta Capital、BVF Partners、Digitalis Ventures等 10月24日，Alpha-9 Oncology今天宣布成功完成超额认购的1.75亿美元C轮融资，以支持其研发管线的推进。该公司已建立了一个多元化的临床期和发现阶段研发管线，涵盖经过验证的靶点和创新靶点。此次C轮融资将用于支持临床阶段候选疗法的人体研究，并推动发现阶段候选药物进入临床开发。此外，C轮融资还将用于扩大研发能力，并持续投资于化学、生产与控制（CMC）和供应链。Alpha-9公司拥有一套独特的结合子、连接子、螯合剂和放射性同位素技术，这些元素在放射性药物开发中都起到关键作用。Alpha-9对每种放射性药物的每个组成部分都进行了优化，以确保药物的选择性、稳定性和有效的载荷递送。 #04 AvenCell Therapeutics完成1.12亿美元B轮融资关键词：CAR-T细胞疗法最新融资：1.12亿美元B轮本轮投资机构：Blackstone Life Sciences、Eight Roads Ventures Japan、F-Prime Capital、NYBC Venture等 10月23日，AvenCell Therapeutics今日宣布完成1.12亿美元的B轮融资。AvenCell是一家处于临床阶段的细胞疗法公司，专注于推进自体和异体可控的CAR-T细胞疗法。AvenCell专注于治疗难以治愈的癌症，其核心项目聚焦于急性髓系白血病（AML），并同时开发针对其他血液系统恶性肿瘤的项目。AvenCell的目标是创建持久性与自体疗法相当或持久性更强的异体细胞，并开发出一种通用且可调控的嵌合抗原受体，使T细胞在输注到患者体内后活性仍然得到控制，并且可以通过添加不同的衔接蛋白靶向不同靶点。这两大平台的结合具潜力使细胞生产不受患者和靶点的限制，从而大幅提高疗法规模化的潜力。 #05 Be Biopharma完成8200万美元融资关键词：B细胞药物最新融资：8200万美元未知轮本轮投资机构：ARCH Venture Partners、Alta Partners、Atlas Venture、Longwood Fund、RA Capital、Takeda Ventures、百时美施贵宝 10月23日，致力于开发B细胞疗法的Be Biopharma公司宣布完成8200万美元的融资，获得的资金将用于实现其用于治疗血友病B的主打项目BE-101的临床概念验证，并推进其用于治疗低磷酸酶症（HPP）的候选药物BE-102的开发。这两个项目均基于该公司强大且高效的B细胞药物（BCM）平台，该平台利用基因编辑技术改造B细胞，使其能够持续产生治疗性蛋白质，最终开发出具有持久性、可滴定且可重复给药的候选药物，无需预处理，具有成为潜在“best-in-class”基因疗法的潜力。 #06 Epitopea完成3100万美元pre-A轮融资关键词：癌症免疫疗法最新融资：3100万美元Pre-A轮本轮投资机构：Advent Life Sciences、CTI Life Sciences、Cambridge Innovation Capital等 10月24日，Epitopea宣布完成3100万美元pre-A轮融资。Epitopea通过靶向一类新的未开发的肿瘤特异性抗原，开发可及现货型基于RNA的免疫疗法。该公司的技术平台利用免疫肽组学、基因组学和生物信息学，可以识别隐藏在癌症“垃圾”DNA中的异常表达的肿瘤特异性抗原（aeTSA）。公司首席执行官Alan C.Rigby博士表示，融资将支持临床前实体瘤研究，并加速公司基于RNA的免疫疗法的近期临床开发计划，最终向临床阶段过渡，并在2026年前将其RNA癌症免疫疗法进行临床交付。读者们请星标⭐创鉴汇，第一时间收到推送免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。更多数据内容推荐点击“在看”，分享创鉴汇健康新动态

IPO临床1期抗体药物偶联物临床2期放射疗法

2024-10-25

·EndPoints

Septerna bags $288M upsized IPO for GPCR drugs

Nascent clinical biotech Septerna added to the slight uptick in IPO fervor this fall with its $288 million Nasdaq listing on Friday. Investors seemed enthused by the prospects of the GPCR biotech. They ate up five million additional shares than Septerna had originally planned to sell in the IPO, and the Bay Area startup priced its public debut at $18 per share $SEPN , or $1 above the high end of the $15 to $17 range it marketed to investors this week. It landed a valuation of about $743 million based on its number of outstanding shares. The drug developer entered the clinic just last month with a Phase 1 healthy volunteer study of SEP-786 in Australia. It anticipates data in mid-2025 and will then move to additional studies in the US, Canada, Europe and other places, according to the company’s IPO filings. Septerna seeks to be the first to create an oral medicine for patients with hypoparathyroidism, a condition that impacts about 100,000 people in the US and impairs the body’s ability to regulate calcium and phosphorus levels. The rare condition has been an active area for researchers and drug developers in recent years. Takeda pulled its drug Natpara from the market, Ascendis Pharma snagged an FDA approval for Yorvipath this summer, and AstraZeneca bought a Phase 3 biotech for up to $1.05 billion this spring. MBX Biosciences, meanwhile, went public last month while in Phase 2 with its candidate. The 68-employee biotech also plans to enter the clinic with another oral small molecule for an inflammatory skin disease known as chronic spontaneous urticaria. Beyond that, Septerna has ambitions to make GPCR medicines for type 2 diabetes and obesity, which has become a hot area for nearly every large pharma and a whole new crop of biotechs thanks to the success of GLP-1 drugs. The biotech drew back the curtains in 2022 based on Nobel Prize-winning work out of GPCR pioneer Robert Lefkowitz. It secured $100 million for that launch round and then came back with a $150 million Series B a year later. Its biggest investors — all owning 5% or more — are Third Rock Ventures, Samsara BioCapital, RA Capital, Deep Track, Invus, BVF and Goldman Sachs’ West Street Life Sciences. At the end of June, Septerna had $143 million in working capital, according to its IPO paperwork.

临床1期IPO并购上市批准