Details

Autor(en) / Beteiligte

• Spicer, AJS
• Venermo, MV
• Hakovirta, HH
• Jalkanen, JMJ

Titel

Induction of CD73 prevents death after emergency open aortic surgery

Ist Teil von

• Cardiovascular research, 2022-06, Vol.118 (Supplement_1)

Erscheinungsjahr

2022

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Faron Pharmaceuticals Ltd Background Cluster of differentiation (CD73) has been a focus of drug development in immuno-oncology for numerous years now. This however disregards the major role of CD73 in inflammatory conditions by the conversion of the majorly conserved and pro-inflammatory, adenosine triphosphate (ATP) to the equally conserved and anti-inflammatory, adenosine. Therefore the induction of CD73 for conditions of major inflammation would occur such as during times of ischemia post major surgery would be therapeutically beneficial. The therapeutic induction of CD73 has previously been shown in other inflammatory condtions by utilising intravenous interferon beta. A ruptured abdominal aortic aneurysm (RAAA) is a medical emergency. Whilst rarely scene now due to improvements to screening, the only lifesaving treatment remains to be is immediate aortic surgery. Half of RAAA patients die before reaching the hospital and despite successful surgery another 30-40% of these patients die post-surgery in intensive care due to multi-organ failure (MOF). The cause of MOF is systemic inflammatory response is brought forth by inflammatory mediators such as ATP, that are released from stressed and dying cells which perpetuate the cycle of inflammation. Purpose Can intravenous interferon beta-1a induce CD73 production and improve survival after emergency open surgery for a ruptured abdominal aortic aneurysm? Methods A multi-center phase II double-blind, randomised, parallel group comparison of the efficacy and safety of intravenous interferon beta-1a vs. placebo for the induction of CD73 to prevent death after open surgery for an infra-renal ruptured abdominal aortic aneurysm Results The initial aim of the trial, better RAAA survival after emergency surgery with INF beta-1a treatment could not be demonstrated due to the under powering of the trial. Nevertheless, the anticipated target mechanism, up-regulation of CD73 was associated with 100% survival. In tandem, both neutralising antibodies and systemic glucocorticoid blocked the up-regulation of CD73. Conclusion Contrary to the initial hypothesis IV IFN beta-1a did not prevent post operative RAAA mortality. Further studies are required to draw definitive conclusions as the clinical trial had to be stopped and did not reach the expected number of participants. Future trials should take into account the potential interaction with glucocorticoids and interferon beta-1a neutralising antibodies. Nonetheless, the anticipated target mechanism of up-regulation of CD73 was associated with survival and is a highly potential molecule to target to improve post-operative RAAA Survival