Activated-platelet targeting of CD39 as a potential way forward
| العنوان: | Activated-platelet targeting of CD39 as a potential way forward |
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| المؤلفون: | Karlheinz Peter, Jan David Hohmann |
| المصدر: | Hämostaseologie. 36:17-25 |
| بيانات النشر: | Georg Thieme Verlag KG, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Drug, media_common.quotation_subject, Hemorrhage, 030204 cardiovascular system & hematology, Pharmacology, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Bleeding time, Antithrombotic, Animals, Humans, Medicine, Platelet, Molecular Targeted Therapy, Platelet activation, Receptor, media_common, medicine.diagnostic_test, business.industry, Apyrase, Thrombosis, Hematology, medicine.disease, Adenosine, Rats, Treatment Outcome, 030104 developmental biology, Drug Design, Immunology, business, Platelet Aggregation Inhibitors, medicine.drug |
| الوصف: | SummaryAntiplatelet therapy is given to millions of patients and has saved numerous lives. However, it is also associated with complications including fatal bleedings. Clinically used antiplatelet drugs seem to follow the rule of an inherent link of improved anti-thrombotic potency with increased risk of bleeding complications. Therefore, there is an ongoing quest to develop drugs that are able to break this link that has prevented many patients from receiving antiplatelet protection and has resulted in substantial mortality and morbidity. We describe a new antiplatelet approach that is based on an recombinant antibody protein, a drug format that has recently attracted major interest. Two unique components are genetically combined in this molecule: 1) The ecto-nucleoside triphosphate diphosphohydrolase NTPDase CD39, which enzymatically degrades ATP and ADP to AMP, which is then further degraded to adenosine by the endothelially expressed CD73. Thereby, the platelet activating ADP is reduced and replaced by the platelet inhibiting adenosine resulting in a strong antiplatelet effect. 2) A single-chain antibody (scFv) that specifically binds to the activated GPIIb/IIIa receptor and thus allows targeting to activated platelets. The described fusion protein results in strong enrichment of CD39’s antiplatelet effect, resulting in potent inhibition of platelet adhesion and aggregation and thrombosis in mice. The activated platelet targeting allows using a low systemic concentration that does not interfere with normal haemostasis and thus does not cause bleeding time prolongation in mice. Conclusion: We describe a new antiplatelet approach that promises to deliver strong localized antithrombotic effects without associated bleeding problems. |
| تدمد: | 2567-5761 0720-9355 |
| DOI: | 10.5482/hamo-14-12-0085 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fcf1ae5daa77d5589cdc3f3f45f7a96d https://doi.org/10.5482/hamo-14-12-0085 |
| رقم الانضمام: | edsair.doi.dedup.....fcf1ae5daa77d5589cdc3f3f45f7a96d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25675761 07209355 |
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| DOI: | 10.5482/hamo-14-12-0085 |