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

大约一半的肾移植患者在新器官的恢复过程中会遇到延迟，这使他们面临更大的风险，因为炎症、排斥和疤痕而过早失去肾脏。我们发明了一种抗炎疗法，针对肾脏中产生的炎症系统的关键成分。这种特殊成分被称为“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，补体蛋白会转而反对被移植的器官。我们的解决方案是抑制补体系统，借用自然保护来防止自残。成品被称为“微概念”。它有一个独特的设计，其中天然补体抑制剂CR1（意思是补体受体1型）被克隆并设计成有尾巴。尾巴可以让我们将治疗药物植入供体肾脏，在植入受体肾脏后，它会被保留并保护器官。在实验动物身上进行的研究表明，接受过治疗的肾脏恢复得更好，这提高了使用损伤较小的肾脏进行临床移植的前景，并使供体器官的寿命更长。这种治疗方法已经在人体上进行了安全性评估，没有出现安全问题。一项随机对照试验将确定它是否能够降低移植物延迟功能的发生率，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是否能改善肾脏和受体的寿命，以及对NHS来说是否具有成本效益。这是至关重要的，因为供体器官供应短缺，而功能延迟的移植数量已经增加，而且随着最近立法的变化，允许器官捐赠的推定同意，移植数量可能会进一步增加。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疾病。这一提议将进一步证明，使用消炎药的“器官绘画”将提高治疗效果，而不会产生普遍的副作用。

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.