权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Efficacy of Mirococept (APT070) for Preventing Ischaemia-Reperfusion Injury associated with Kidney Transplantation-2 (EMPIRIKAL-2)

Mirococept (APT070) 预防肾移植相关缺血再灌注损伤的功效-2 (EMPIRIKAL-2)

基本信息

批准号：
MR/V038281/1
负责人：
Steven Sacks
金额：
$ 578.86万
依托单位：
King's College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FV038281%2F1
关键词：
Efficacy Mirococept APT070 Preventing Ischaemia

项目摘要

About half of all kidney transplant patients experience a delay in the recovery of the new organ, and this puts them at greater risk of losing the kidney prematurely through inflammation, rejection and scarring. We have invented an anti-inflammatory treatment that targets a key component of the inflammatory system produced in the kidney. The particular component is called 'complement' due to its natural ability to complement the immune response against infection. In the absence of infection, however, complement proteins can turn against the organ being transplanted. Our solution is to inhibit the complement system, borrowing from natural protection against self-injury. The finished product is called Mirococept. It has a unique design where the natural complement inhibitor CR1 (meaning complement receptor type 1) has been cloned and engineered to have a tail. The tail allows us to plant the therapeutic in the donor kidney, where it is retained and protects the organ following its implantation into the recipient. Work in laboratory animals has shown that treated kidneys undergo better recovery, raising the prospect of using less-damaged kidneys for clinical transplantation and giving the donor organ a longer life. The treatment has already undergone safety evaluation in humans and no safety concerns have arisen. A randomised controlled trial would determine whether it fulfils the promise to reduce the rate of delayed graft function and identify the most effective dose. The proposed trial will be a springboard for wider development to determine whether Mirococept improves the lifespan of the kidney and the recipient and is cost-effective for the NHS. This is crucial since donor organs are in short supply and the number of transplants with delayed function has increased and is likely to rise further with the recent change in legislation allowing presumed consent for organ donation. The potential indications for complement inhibitors go wider than organ transplantation and include conditions such as coronary artery surgery, age-related blindness and current clinical trials for COVID-19 lung inflammation. The proposal would add proof to the idea that 'organ painting' with anti-inflammatory drugs will improve the effectiveness of treatment without causing general side effects.

大约一半的肾移植患者在新器官的恢复过程中会出现延迟，这使他们面临更大的风险，因为炎症、排斥反应和疤痕而过早失去肾脏。我们发明了一种抗炎治疗方法，其目标是肾脏中产生的炎症系统的关键组成部分。这种特殊的成分被称为“补体”，因为它具有补充抗感染免疫反应的天然能力。然而，在没有感染的情况下，补体蛋白可能会对抗被移植的器官。我们的解决方案是抑制补体系统，借用自然保护免受自我伤害。成品被称为Mirococept。它有一个独特的设计，其中天然补体抑制剂CR 1（意思是补体受体1型）已被克隆和工程化，有一个尾巴。尾部允许我们将治疗剂植入供体肾脏，在移植到受体后，它被保留并保护器官。在实验室动物身上的工作表明，经过处理的肾脏恢复得更好，这提高了在临床移植中使用损伤较小的肾脏并使供体器官寿命更长的前景。该治疗已经在人体中进行了安全性评估，没有出现安全性问题。一项随机对照试验将确定它是否实现了降低移植物功能延迟恢复率的承诺，并确定最有效的剂量。拟议的试验将成为更广泛发展的跳板，以确定Mirococept是否改善了肾脏和受体的寿命，并且对NHS具有成本效益。这一点至关重要，因为捐赠器官供应短缺，功能延迟的移植数量有所增加，而且随着最近立法的变化，允许假定同意捐赠器官，这种情况可能会进一步增加。补体抑制剂的潜在适应症比器官移植更广泛，包括冠状动脉手术、年龄相关性失明和目前针对COVID-19肺部炎症的临床试验等情况。这项提议将进一步证明，用抗炎药物“器官彩绘”将提高治疗效果，而不会引起一般的副作用。