Medical device organisation MediSieve is receiving two grants from Innovate UK for two-year projects beginning this year, totalling £1.56 million.
One large biomedical catalyst grant will progress development of a severe sepsis product, developing five magnetic particles to remove different sepsis targets. Another SRBI grants will allow further focus on one of those particles and how it can be used to remove anti-microbial resistant (AMR) bacteria from a patient’s bloodstream.
Sepsis research is of high priority because, with mortality over 30% and antibiotic therapies increasingly at risk from antimicrobial resistance, its human and economic impact have never been more concerning. The infection causes the body to attack its own organs and tissues and affects 20 million people globally each year. The Biomedical Catalyst (BMC) project aims to develop a multi-target magnetic blood filtration treatment that is complimentary to antibiotics, working to address the LPS and cytokines that antibiotics release and which exacerbate the immune response and elevate cytokine levels.
Dr George Frodsham, CEO and founder of MediSieve, said: "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 2019.
"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, which aggravate the immune response, causing the over-production of inflammatory cytokines and a 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 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.
"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."
The SBRI project explores an alternative to antibiotics to reduce the level of bacteria in the bloodstream of AMR sepsis patients, with the added benefit of LPS removal as a secondary effect.
Both projects involve distinct experimental pathways which can be delivered simultaneously with the added benefit that areas of synergy and overlap reduce workload. Whilst the SBRI project focuses exclusively on targeting and removing E. coli, the BMC project does not include any E. coli or other bacterial testing. The SBRI project includes a clinical trial, whereas the BMC does not.