Keynote lecture 1

Professor Bruce Zuraw: How did we get to here? 

Professor Zuraw, Professor of Medicine at the University of California in San Diego, began with the near-impossible task of reviewing the entire history of angioedema in ten minutes. To try and achieve this, he called to mind the idea of a recipe. He suggested the preparation time was almost 150 years, with the basic science of bradykinin and kallikrein published in the 1940s and early 1960s. The contact system has been understood for around 20 years, and Dr Bork’s genomic work was a major advance. Ultimately, all this knowledge has raised more questions, such as HAE with normal C1 inhibitor and HAE of unknown etiology. He recognized the work done not just by scientists but also by patient advocates to get pharmaceutical companies engaged, and these companies have taken the 1983 Orphan Drug Act as a spur to develop drugs that offer patients the chance of a normal life.

‘Everyone benefits when patients are included as equal partners, and effective collaboration between clinical investigators, basic scientists, patients, and pharma really is a good recipe to get outstanding outcomes.’

– Dr Bruce Zuraw

Dr Zuraw then turned the stage over to Professor Alvin Schmaier, Professor of Medicine at Case Western Reserve University, USA.

Professor Alvin Schmaier: Bradykinin and where the science could take us

Starting where Dr Zuraw left off, Prof Schmaier asked: What does bradykinin really do? He suggested that while science now knows it is elevated in HAE, what happens in an acute attack hasn’t really been well demonstrated, and more studies are needed. He spoke to the underlying genetic variation in HAE and the work conducted to date to understand better the contact system mentioned by Prof Zuraw. Put simply, though, Prof Schmaier said: “If we decrease C1 inhibitor, we increase bradykinin formation. If we increase the C1 inhibitor, bradykinin is less.” It matters hugely in HAE, but bradykinin is also a key mediator in other conditions, such as cerebral malaria. Looking to the future, Prof Schmaier concluded:

• More work is needed to understand the mechanisms of uncommon angioedemas
• We need to understand if bradykinin is the primary mediator of these disorders
• There is potential to develop new antagonists in the kallikrein-kinin system/VEGF systems and agonists to the angiopoietin 1/TIE2 and S1P/S1Pr1 systems
• The search goes on for other swelling disorders, perhaps even those associated with cancer metastasis