TY - JOUR
T1 - The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS
AU - Grigoropoulos, Ioannis
AU - Tsioulos, Georgios
AU - Kastrissianakis, Artemis
AU - Shapira, Shiran
AU - Green, Orr
AU - Rapti, Vasiliki
AU - Tsakona, Maria
AU - Konstantinos, Thomas
AU - Savva, Athina
AU - Kavatha, Dimitra
AU - Boumpas, Dimitrios
AU - Syrigos, Konstantinos
AU - Xynogalas, Ioannis
AU - Leontis, Konstantinos
AU - Ntousopoulos, Vasileios
AU - Sakka, Vissaria
AU - Sardelis, Zafeiris
AU - Fotiadis, Andreas
AU - Vlassi, Lamprini
AU - Kontogianni, Chrysoula
AU - Levounets, Anastasia
AU - Poulakou, Garyfalia
AU - Gaga, Mina
AU - MacLoughlin, Ronan
AU - Stebbing, Justin
AU - Arber, Nadir
AU - Antoniadou, Anastasia
AU - Tsiodras, Sotirios
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Introduction: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. Methods: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. Results: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. Conclusions: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.
AB - Introduction: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. Methods: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. Results: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. Conclusions: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.
KW - ARDS exosomes
KW - CD24
KW - Covid-19
KW - EXO-CD24
KW - Phase IIb
UR - http://www.scopus.com/inward/record.url?scp=85189081500&partnerID=8YFLogxK
U2 - 10.1186/s12931-024-02759-5
DO - 10.1186/s12931-024-02759-5
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C2 - 38561798
AN - SCOPUS:85189081500
SN - 1465-9921
VL - 25
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 151
ER -
