Research by Professor Paul Barlow and group has opened up the possibility of new therapies that use complement-control protein factor H (FH) to prevent damage to human cells.
The challenge: understanding the complement system for development of new therapies
The blood-borne proteins of the complement system defend the body against invading microbes and clear debris arising from damaged or dying human cells. Inappropriate or disproportionate activation of the complement system, however, causes numerous autoimmune, degenerative and inflammatory diseases, as well as undesirable inflammatory responses to medical interventions.
Factor H (FH) is a key complement-regulating protein that protects healthy “self” tissue from attack by the complement system. The ability to control complement attack using FH presents exciting opportunities for the development of therapies. In order to realise these, an in-depth knowledge of the structure and mode of action of FH is needed.
Discovery of enhanced FH action to stop complement attack
Barlow’s research has provided atomic-level understanding of how FH interacts with molecular partners that are crucial to its protective function1. With key input from colleague Dr Andrew Herbert, the group discovered how some bacteria are able to hijack FH to protect themselves against complement-system attack2. This inspired them to exploit bacterial FH-binding proteins to stop the complement-triggered damage caused when blood comes into contact with foreign surfaces such as dialysis filters, stents and catheters, or transplanted organs.
Formation of Invizius to target cardiovascular damage caused by dialysis
Invizius spun out from the University of Edinburgh in April 2018 to develop this breakthrough technology to reduce cardiovascular damage caused by dialysis, which ultimately reduces average life expectancy for dialysis patients by two thirds. The company’s H-Guard® priming solution coats the dialysis filter and very tightly sequesters FH from the patient’s blood to render the device invisible to the immune system. This approach is unique in preventing, at source, the blood’s reaction to the foreign body, rather than treating its consequences. H-Guard® presents the first major innovation in dialysis filter haemocompatibility since the 1980s.
Almost £4M of investment has been raised to support the development of the Invizius technology. Already, ex vivo testing in rigs that model the dialysis blood circuit has shown a marked reduction in complement activation when the dialysis filter circuit is coated with H-Guard®. Importantly, this reduction occurs in the crucial first hour of contact with the filter, which is known to trigger the maximum immune response.
In recognition of their innovative solution to a major health need, Invizius have been named one of the “Fierce 15” Med Tech Companies of 2018, as well as ‘Best Innovative MedTech’ at the 2018 OBN Awards.
- H.P. Morgan, C.Q. Schmidt, M. Guariento, B.S. Blaum, D. Gillespie, A.P. Herbert, D. Kavanagh, H.D. Mertens, D.I. Svergun, C.M. Johansson, D. Uhrín, P.N. Barlow and J.P. Hannan, “Structural basis for engagement by complement Factor H of C3b on a self-surface”, Nat. Struct. Mol. Biol., 2011, 18, 463-470. DOI: 10.1038/nsmb.2018.
- A.P. Herbert, E. Makou, Z.A. Chen, H. Kerr, A. Richards, J. Rappsilber and P.N. Barlow, “Complement Evasion Mediated by Enhancement of Captured Factor H: Implications for Protection of Self-Surfaces from Complement”. J. Immunol., 2015, 195, 4986-4998. DOI: 10.4049/jimmunol.1501388.