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经历了新器官恢复的延迟，这使得他们面临着更大的风险，即通过炎症、排斥反应和疤痕过早失去肾脏。我们发明了一种抗炎疗法，针对肾脏产生的炎症系统的一个关键成分。这种特殊的成分被称为补体，因为它有天然的能力来补充免疫反应，防止感染。然而，在没有感染的情况下，补体蛋白可能会对被移植的器官不利。我们的解决方案是抑制补体系统，借助于防止自我伤害的自然保护。最终产品被称为米罗科普。它有一个独特的设计，其中天然补体抑制物CR1(意思是补体受体1型)已经被克隆并被设计成有一个尾巴。尾巴允许我们将治疗药物植入供体肾脏，在移植到受者体内后，它被保留在那里并保护器官。在实验室动物身上的研究表明，经过治疗的肾脏恢复得更好，这增加了使用受损较少的肾脏进行临床移植的可能性，并使捐赠者的器官寿命更长。这种治疗已经在人体上进行了安全性评估，没有出现任何安全问题。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发生率的承诺，并确定了最有效的剂量。拟议中的试验将成为更广泛发展的跳板，以确定米罗西普是否延长了肾脏和接受者的寿命，并对NHS来说是具有成本效益的。这一点至关重要，因为捐赠器官供不应求，功能延迟的移植数量有所增加，而且随着最近允许对器官捐赠推定同意的立法的改变，这一数字可能会进一步上升。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、老年性失明以及目前针对新冠肺炎肺部炎症的临床试验。这项提议将为用抗炎药物进行器官涂抹将提高治疗效果而不会引起一般副作用的想法提供证据。

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.