Dr Wioleta Zelek: Race Against Dementia Fellow and UK DRI Emerging Leader, Cardiff University

Dr Wioleta Zelek is an early career researcher focussed on the complement system, its biology and function and roles in diseases with the ultimate aim of identifying new drugs targeting complement. She trained in Chemistry and after several years in the Biotech sector, returned to academia and undertook a PhD in Immunology, focused on the complement system. During her PhD, and Fellowships (ISSF Wellcome Trust, Health and Care Research Wales) she has developed a toolbox of novel complement inhibitors, including patent protected drug candidates (PCT/EP2020/073430) and other tool reagents enabling the study of complement in animal disease models. She has recently joined the Cardiff DRI as a UK DRI Emerging Leader. Dr Zelek’s goal over the course of the Fellowship is to develop a brain penetrant anti-complement drug candidates to target neuroinflammation, the critical driver of pathology in AD.

The complement system is a potent driver of inflammation in many diseases, including Alzheimer’s where inflammation is a major factor in the pathogenesis. I hope to develop a new approach to AD therapy; brain penetrant anti-complement drug(s), providing better ways of treating AD and other dementias. I am very grateful and inspired to be part of the ARUK-RAD Team. I am enthused by the philosophy of team work that underpins RAD and look forward to applying the RAD principles to my research.

Dr Wioleta Zelek: Race Against Dementia Fellow and UKDRI Emerging Leader

Research Summary

Complement is a system of proteins in blood that exists to counter bacterial infections, either by directly killing bacteria or provoking white blood cells to eat them. The direct-killing part of complement is a protein complex called MAC which bursts bacteria and human cells alike by poking holes in their surfaces like a pinprick in a balloon. Leaking cells cause lots of inflammation. Inflammation is implicated in many diseases, including Alzheimer’s. I want to test the idea that overactivity in MAC and the inflammation it causes is an important driver of Alzheimer’s disease. I will develop new ways of targeting MAC in ways which will prevent the “hole-punching” activity that is most harmful to our own cells and the most inflammatory, while leaving intact the important roles of complement in killing bacteria. I will generate MAC-blocking drugs capable of entering the brain that can stop MAC-driven brain inflammation. I will develop these agents using test-tube models of the barrier between the blood and brain, select the best agents from these studies and provide a proof-of-concept for their use in Alzheimer’s by testing them in appropriate animal models, laying the groundwork for future human therapies.