Magnetic Blood Filtration for the Treatment of Sepsis

磁性血液过滤治疗脓毒症

• 批准号: 104812
• 金额: $ 126.13万
• 依托单位: MEDISIEVE LTD
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=104812
• 关键词: Magnetic; Blood; Filtration; Treatment; Sepsis

MediSieve is a medical device company developing "magnetic blood filtration": a revolutionary treatment for blood-borne diseases which removes pathogens directly from the bloodstream. Our technology is like dialysis, circulating a patient's blood through an external loop to remove disease causing targets. While dialysis relies on non-specific size based filtration, MediSieve uses magnetic particles coated with antibodies (Ab-MP) to target specific components, and a magnetic filter to extract them.The patented MediSieve Filter (MF) can safely remove magnetic components from the bloodstream. It is already developed as a treatment for severe malaria (Ab-MPs are not required for malaria, since malaria infected cells exhibit naturally occurring magnetic properties). The MF has completed pre-clinical testing and will enter first-in-man clinical trials in 2018\.This project concerns the development of the Ab-MP to apply our technology to Sepsis. Sepsis is caused by an infection that creates a dysregulated immune response which can escalate to septic shock. The destruction of bacteria by the immune system or antibiotics creates large quantities of endotoxins (LPS), which aggravate the immune response, causing the over-production of inflammatory cytokines and cascade towards septic shock. Antibiotics kill pathogens, but do not remove them from the bloodstream, so the immune system's overreaction continues.Our Ab-MPs target LPS, gram-negative bacteria, specific cytokines and a damage associated molecular patterns (DAMP) rapidly reducing the levels in a patient's bloodstream. Used in combination with antibiotics, it could help eliminate the infection, and reverse the escalation to septic shock. Treatment of sepsis with antibiotics increases the LPS load in the bloodstream, since LPS persist after the pathogens have been killed. LPS, inflammatory cytokine and DAMP levels correlate with clinical outcomes, and their removal would be beneficial in helping to treat the disease.Sepsis is one of the world's leading causes of death, exerting a huge human and economic toll. Sepsis kills 44,000/year in the UK. Globally, there are over 20M total cases and over 6M newborns and children are affected annually. Global incidence has been increasing rapidly. With mortality over 30%, there is a clear need for better treatments especially as current antibiotic therapies are increasingly vulnerable to antimicrobial resistance.This project will focus on the development of the Ab-MP to target LPS, cytokines and DAMP, proving their safety and efficacy in both laboratory and pre-clinical safety and efficacy trials, and performing the biocompatibility testing required in order to progress the treatment to first-in-man clinical trials.

MediSieve是一家开发“磁性血液过滤”的医疗设备公司：这是一种革命性的血液传播疾病治疗方法，可直接从血液中去除病原体。我们的技术就像透析，通过外部循环使患者的血液循环，以去除致病目标。虽然透析依赖于非特定尺寸的过滤，但MediSieve使用涂有抗体的磁性颗粒（Ab-MP）来靶向特定成分，并使用磁性过滤器来提取它们。获得专利的MediSieve过滤器（MF）可以安全地去除血液中的磁性成分。它已经被开发用于治疗严重的疟疾（疟疾不需要Ab-MP，因为疟疾感染的细胞表现出天然存在的磁性）。MF已完成临床前测试，并将于2018年进入首次人体临床试验。该项目涉及Ab-MP的开发，以将我们的技术应用于脓毒症。脓毒症是由感染引起的，这种感染会产生失调的免疫反应，这种免疫反应可以升级为脓毒性休克。免疫系统或抗生素对细菌的破坏会产生大量的内毒素（LPS），这些内毒素会加剧免疫反应，导致炎症细胞因子的过度产生并导致败血性休克。抗生素杀死病原体，但不能将其从血液中清除，因此免疫系统的过度反应仍在继续。我们的Ab-MP针对LPS、革兰氏阴性菌、特定细胞因子和损伤相关分子模式（DAMP），迅速降低患者血液中的水平。与抗生素联合使用，它可以帮助消除感染，并逆转感染性休克的升级。用抗生素治疗脓毒症会增加血流中的LPS负荷，因为LPS在病原体被杀死后仍存在。LPS、炎性细胞因子和DAMP水平与临床结果相关，并且它们的去除将有助于帮助治疗疾病。脓毒症是世界上主要的死亡原因之一，造成巨大的人类和经济损失。败血症在英国每年杀死44，000人。在全球范围内，每年有超过2000万例病例，超过600万新生儿和儿童受到影响。全球发病率迅速上升。随着死亡率超过30%，特别是当前抗生素治疗越来越容易受到抗生素耐药性的影响，显然需要更好的治疗方法。本项目将重点开发针对LPS，细胞因子和DAMP的Ab-MP，在实验室和临床前安全性和有效性试验中证明其安全性和有效性，并进行所需的生物相容性测试，以便将治疗进展到首次人体临床试验。