Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients
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Published:2023-09-13
Issue:9
Volume:11
Page:2523
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ISSN:2227-9059
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Container-title:Biomedicines
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language:en
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Short-container-title:Biomedicines
Author:
Green Orr12, Shenberg Gil1, Baruch Roni23, Argaman Lihi1, Levin Talya1, Michelson Ian12, Hadary Ruthy4, Isakovich Boris5, Golos Miri6, Schwartz Reut27, MacLoughlin Ronan89ORCID, Adi Nimrod27, Arber Nadir12, Shapira Shiran12
Affiliation:
1. Health Promotion Center and Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel 3. Department of Kidney Transplantation, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel 4. Department of Internal Medicine C, Meir Medical Center, Kefar-Saba 4428164, Israel 5. Intensive Care Unit, Hillel Yaffe Medical Center, Hadera 3820302, Israel 6. Carmel Medical Center, Haifa 3436212, Israel 7. Anesthesia and Intensive Care Unit, Tel-Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel 8. School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, D02 YN77 Dublin, Ireland 9. School of Pharmacy and Pharmaceutical Sciences, Trinity College, D02 PN40 Dublin, Ireland
Abstract
Rationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. Measurements and Main Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. Conclusions: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings.
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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