AUSTIN, Texas, August 27, 2018 (GLOBE NEWSWIRE) – XBiotech Inc. (NASDAQ: XBIT) today announced the release of results indicating that leukocyte-derived Interleukin-1 alpha (IL-1⍺) is the cause clots that can cause a heart attack or stroke. The research was led by a world-renowned cardiovascular researcher, Dr. Peter Libby, Professor Mallinckrodt of Medicine at Harvard Medical School and Clinical Cardiologist at Brigham and Women’s Hospital. Dr. Libby’s team has discovered that leukocytes called neutrophil granulocytes can produce IL-1⍺ that can potentially cause fatal strokes in patients with heart disease. This discovery allows to consider a new treatment with bermekimab,
The results describe for the first time an intriguing mechanism in which extracellular neutrophil traps (PEN), released by neutrophil granulocytes, are filled with IL-1⍺ capable of activating arterial wall cells which, in turn, activate coagulation mechanisms and recruit other leukocytes. The publication presents the work of Dr. Folco and Dr. Mawson, colleagues of Dr. Libby, who describe how in certain types of heart disease, in which blood vessels become partially blocked by atherosclerotic plaques, the activation of blood vessels by IL-1⍺ on PEN can be an important contributing factor to heart attacks. These results are among the first to provide a clear mechanism for triggering heart attacks by neutrophils and at the same time offer the possibility of treatment by blocking IL-1⍺. These results also suggest treatment opportunities for other inflammatory diseases in which neutrophils, and more specifically PEN, play a role in the pathology, such as cancer and pulmonary, autoimmune and gastrointestinal diseases.
According to Dr. Libby: “Our data suggest that IL-1⍺-associated vascular endothelial cell activation can not only amplify, support, and spread local vascular inflammation, but also promote thrombosis. We believe that these results will have very important clinical implications. “
For his part, John Simard, CEO of XBiotech said, “Dr. Libby’s discovery provides a new mechanism for understanding where and why we could target IL-1 to treat inflammatory diseases. This is fundamental progress in biology and a major step for us. “
Les résultats du Dr Libby sont publiés en ligne dans le journal de l’American Heart Association (AHA). L’article intitulé « Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1α and Cathepsin G », est publié dans le numéro du mois d’août de Arteriosclerosis, Thrombosis, and Vascular Biology.
Coronary artery thrombus can be caused by rupture or erosion of the plate 1 . Superficial erosion of plaque causes up to one-third of all acute coronary syndromes 2,3 . Atheromatous plaques prone to erosion, rather than lesions with stable or fracture-prone characteristics, associate with extracellular neutrophil traps (PEN) 4. The study, conducted in Dr. Libby’s lab, probed the influence of PENs on endothelial cell (EC) functions related to thrombosis associated with erosion. These data indicate that exposure of human saphenous vein EC (HSVEC) to NET contributes to increased expression of adhesion molecules on the surface of endothelial cells such as VCAM-1 and ICAM-1, which may participate in atherogenesis. In addition, pretreatment of NETs with bermekimab, an anti-IL-1⍺ neutralizing antibody, or an IL-1R antagonist, but not with an anti-IL-1β-neutralizing antibody, blocked the initiation of VCAM-1, ICAM-1 and TF expression, each related to coronary thrombosis 5,6. In conclusion, NETs increase in vitro thrombogenicity by an IL-1⍺-mediated response. These data indicate a potentially important role for treatment with bermekimab for certain heart diseases and other neutrophil-mediated diseases.
About True Human ™ Therapeutic
Antibodies XBiotech’s True Human ™ antibodies are derived without modification from people with natural immunity to certain diseases. With discovery and clinical programs across multiple therapeutic areas, XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight the disease with increased safety, efficacy and efficacy. tolerance.
About XBiotech
XBiotech is a fully integrated global bioscience company pioneering the discovery, development and commercialization of therapeutic antibodies based on its proprietary True Human ™ technology. XBiotech is currently working to advance a major pipeline of antibody therapeutics aimed at redefining the standards of care in oncology, inflammatory diseases and infectious diseases. Headquartered in Austin, Texas, XBiotech is also leading the development of innovative biotech manufacturing technologies designed to produce faster, more cost-effective and more flexible new therapies that are urgently needed by patients around the world. For more information, visit www.xbiotech.com.
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1 Crea F, Libby P. Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment. Circulation 2017; 136: 1155-1166.
2 Franck G, et al. Flow Mediates Disruption Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice – Implications for Superficial Erosion. Circ Res 2017; 121: 31-42.
3 Libby P. Superficial erosion and precision management of acute coronary syndromes: not one-size-fits-all. Eur Heart J. 2017; 38 (11): 801-803. doi: 10.1093 / eurheartj / ehw599.
4 Keelboat T et al. TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion. Eur Heart J. 2015 Jun 7; 36 (22): 1394-404. doi: 10.1093 / eurheartj / ehv044. Epub 2015 Mar 8.
5 Tousoulis D , et al. Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Heart. 2003; 89 (9): 993-7.
6 Folco EJ, Mawson TL, Vromman A et al. Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production through Interleukin-1a and Cathepsin G. Arteriosclerosis, Thrombosis, and Vascular Biology 2018; 2018; 38: 1901-1912.
