Respiratory Research (Apr 2024)

The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS

  • Ioannis Grigoropoulos,
  • Georgios Tsioulos,
  • Artemis Kastrissianakis,
  • Shiran Shapira,
  • Orr Green,
  • Vasiliki Rapti,
  • Maria Tsakona,
  • Thomas Konstantinos,
  • Athina Savva,
  • Dimitra Kavatha,
  • Dimitrios Boumpas,
  • Konstantinos Syrigos,
  • Ioannis Xynogalas,
  • Konstantinos Leontis,
  • Vasileios Ntousopoulos,
  • Vissaria Sakka,
  • Zafeiris Sardelis,
  • Andreas Fotiadis,
  • Lamprini Vlassi,
  • Chrysoula Kontogianni,
  • Anastasia Levounets,
  • Garyfalia Poulakou,
  • Mina Gaga,
  • Ronan MacLoughlin,
  • Justin Stebbing,
  • Nadir Arber,
  • Anastasia Antoniadou,
  • Sotirios Tsiodras

DOI
https://doi.org/10.1186/s12931-024-02759-5
Journal volume & issue
Vol. 25, no. 1
pp. 1 – 13

Abstract

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Abstract 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.

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