Magnetic Blood Filtration for the Treatment of Sepsis

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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.