tetano
Editor, Senior Moderator
Respir Res
. 2024 Apr 1;25(1):151.
doi: 10.1186/s12931-024-02759-5. The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS
Ioannis Grigoropoulos[SUP] #[/SUP][SUP] 1 [/SUP], Georgios Tsioulos[SUP] #[/SUP][SUP] 1 [/SUP], Artemis Kastrissianakis[SUP] 1 [/SUP], Shiran Shapira[SUP] 2 3 [/SUP], Orr Green[SUP] 2 [/SUP], Vasiliki Rapti[SUP] 4 [/SUP], Maria Tsakona[SUP] 1 [/SUP], Thomas Konstantinos[SUP] 1 [/SUP], Athina Savva[SUP] 1 [/SUP], Dimitra Kavatha[SUP] 1 [/SUP], Dimitrios Boumpas[SUP] 1 [/SUP], Konstantinos Syrigos[SUP] 4 [/SUP], Ioannis Xynogalas[SUP] 4 [/SUP], Konstantinos Leontis[SUP] 4 [/SUP], Vasileios Ntousopoulos[SUP] 4 [/SUP], Vissaria Sakka[SUP] 4 [/SUP], Zafeiris Sardelis[SUP] 5 [/SUP], Andreas Fotiadis[SUP] 5 [/SUP], Lamprini Vlassi[SUP] 5 [/SUP], Chrysoula Kontogianni[SUP] 5 [/SUP], Anastasia Levounets[SUP] 5 [/SUP], Garyfalia Poulakou[SUP] 4 [/SUP], Mina Gaga[SUP] 5 [/SUP], Ronan MacLoughlin[SUP] 6 7 8 [/SUP], Justin Stebbing[SUP] 9 10 [/SUP], Nadir Arber[SUP] 11 12 [/SUP], Anastasia Antoniadou[SUP] 1 [/SUP], Sotirios Tsiodras[SUP] 1 [/SUP]
Affiliations
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 10[SUP]9[/SUP] or 10[SUP]10[/SUP] 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 (SpO[SUB]2[/SUB]) (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.
Keywords: ARDS exosomes; CD24; Covid-19; EXO-CD24; Phase IIb.
. 2024 Apr 1;25(1):151.
doi: 10.1186/s12931-024-02759-5. The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS
Ioannis Grigoropoulos[SUP] #[/SUP][SUP] 1 [/SUP], Georgios Tsioulos[SUP] #[/SUP][SUP] 1 [/SUP], Artemis Kastrissianakis[SUP] 1 [/SUP], Shiran Shapira[SUP] 2 3 [/SUP], Orr Green[SUP] 2 [/SUP], Vasiliki Rapti[SUP] 4 [/SUP], Maria Tsakona[SUP] 1 [/SUP], Thomas Konstantinos[SUP] 1 [/SUP], Athina Savva[SUP] 1 [/SUP], Dimitra Kavatha[SUP] 1 [/SUP], Dimitrios Boumpas[SUP] 1 [/SUP], Konstantinos Syrigos[SUP] 4 [/SUP], Ioannis Xynogalas[SUP] 4 [/SUP], Konstantinos Leontis[SUP] 4 [/SUP], Vasileios Ntousopoulos[SUP] 4 [/SUP], Vissaria Sakka[SUP] 4 [/SUP], Zafeiris Sardelis[SUP] 5 [/SUP], Andreas Fotiadis[SUP] 5 [/SUP], Lamprini Vlassi[SUP] 5 [/SUP], Chrysoula Kontogianni[SUP] 5 [/SUP], Anastasia Levounets[SUP] 5 [/SUP], Garyfalia Poulakou[SUP] 4 [/SUP], Mina Gaga[SUP] 5 [/SUP], Ronan MacLoughlin[SUP] 6 7 8 [/SUP], Justin Stebbing[SUP] 9 10 [/SUP], Nadir Arber[SUP] 11 12 [/SUP], Anastasia Antoniadou[SUP] 1 [/SUP], Sotirios Tsiodras[SUP] 1 [/SUP]
Affiliations
- PMID: 38561798
- PMCID: PMC10983648
- DOI: 10.1186/s12931-024-02759-5
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 10[SUP]9[/SUP] or 10[SUP]10[/SUP] 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 (SpO[SUB]2[/SUB]) (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.
Keywords: ARDS exosomes; CD24; Covid-19; EXO-CD24; Phase IIb.