Extending Mironid's PDE4 activator programme: Hyperparathyroidism as a second clinical indication

扩展 Mironid 的 PDE4 激活剂计划：甲状旁腺功能亢进作为第二个临床适应症

• 批准号: 10038156
• 金额: $ 63.95万
• 依托单位: MIRONID LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10038156
• 关键词: Extending; Mironid; PDE4; activator; programme

Human parathyroid hormone (PTH) is produced by four parathyroid glands located in the neck and regulates the level of calcium and phosphate in the blood by controlling reabsorption from urine, uptake from the digestive tract and resorption from calcium reservoirs in the bone.Hyperparathyroidism results in excessive release of parathyroid hormone into the blood and is one of the most common endocrine disorders, often caused by either a benign tumour in one or more parathyroid glands or as a secondary consequence of chronic kidney disease. Left untreated, the chronic elevation of PTH in hyperparathyroidism causes a variety of debilitating symptoms and can even become life-threatening when the levels of calcium in the blood become unacceptably high. The prevalence of hyperparathyroidism is increasing as a consequence of rising rates of obesity, diabetes and associated kidney disease.Mironid, a Glasgow based biotech company founded by research teams from Strathclyde and Heriot-Watt Universities, has developed the first molecules that activate particular enzymes called PDE4 long isoforms that normally degrade an important signalling molecule called cAMP. cAMP is usually very tightly regulated but in hyperparathyroidism is over produced in certain locations within the kidney and bone as a result of excessive stimulation by PTH. Mironid's innovation offers a novel approach to targeting hyperparathyroidism at the site of PTH action in the kidney and bone, by increasing the degradation of cAMP, thereby reducing cAMP signalling and allowing better management of the symptoms and pathology of hyperparathyroidism.This proposal aims to build upon a previous successful Innovate UK BMC funded Mironid project (Year 2017: Project No: 102841) that has already resulted in important progress towards treating another kidney disease, Autosomal Dominant Polycystic Kidney Disease, also caused by defective cAMP signalling. As part of this current proposal, new molecules will be tested in translational models of hyperparathyroidism and will be profiled in assays to identify the most appropriate molecule for advanced testing and ultimately for progression into human trials which could begin as early as 2025\.

人甲状旁腺激素（PTH）是由位于颈部的四个甲状腺腺产生的，并通过控制尿液的重吸收，消化道的吸收，从消化道的吸收以及钙储量中的钙储量中的钙含量最终释放中的含量和含量的含量来调节血液中的钙含量最终的含量和含量的含量均产生了多余的含量，从而使血液中的钙的吸收水平和钙的吸收。疾病通常是由一个或多个甲状旁腺中的良性肿瘤引起的，或者是慢性肾脏疾病的第二结果。未经治疗的情况下，甲状旁腺功能亢进症中PTH的慢性升高会引起多种使人衰弱的症状，甚至当血液中的钙水平变得不可接受时，甚至可能会危及生命。 The prevalence of hyperparathyroidism is increasing as a consequence of rising rates of obesity, diabetes and associated kidney disease.Mironid, a Glasgow based biotech company founded by research teams from Strathclyde and Heriot-Watt Universities, has developed the first molecules that activate particular enzymes called PDE4 long isoforms that normally degrade an important signalling molecule called cAMP. cAMP通常受到非常严格的调节，但是在甲状腺功能亢进症中，由于PTH过度刺激，在肾脏和骨骼的某些位置产生了过度。 Mironid的创新提供了一种新颖的方法，可以通过增加营地的退化来靶向肾脏和骨骼的PTH动作部位，从而减少营地信号，从而更好地管理超甲状旁腺功能障碍的症状和病理学。在治疗另一种肾脏疾病，常染色体显性多囊性肾脏疾病方面取得了重要进展，这也是由cAMP信号不良引起的。作为当前建议的一部分，新分子将在甲状旁腺功能亢进症的翻译模型中进行测试，并将在测定中进行介绍，以识别最适合先进测试的分子，并最终以最早的时间为2025年开始进行人体试验。