A Randomized Controlled Trial to Evaluate the Safety and Efficacy of a Novel Inhaled Biologic Therapeutic in Adults with Respiratory Distress Secondary to COVID-19 Infection

Roshon, Michael; Lemos-Filho, Luciano; Cherevka, Holli; Goldberg, Laura; Salottolo, Kristin; Bar‐Or, David

doi:10.1007/s40121-021-00562-z

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Influenced by these observations, clinical studies were designed to investigate the use of inhaled AMP5A for the treatment of the systemic inflammatory response syndrome and respiratory distress associated with COVID-19. Phase I trial results show that AMP5A treatment reduces all-cause COVID-19 mortality 5-fold (mortality of 24% in the standard of care group versus 5% in the AMP5A treatment group) [17].…”

Section: Introductionmentioning

confidence: 99%

AMP5A modulates Toll-like receptors 7 and 8 single-stranded RNA immune responses in PMA-differentiated THP-1 and PBMC

et al. 2022

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Background Dysregulation of antiviral immunity has been implicated in the progression of acute respiratory syndrome coronavirus 2 infection into severe cases of coronavirus disease of 2019 (COVID-19). Imbalances in the inflammatory response drive the overabundant production of pro-inflammatory cytokines and chemokines. The low molecular weight fraction of 5% human serum albumin commercial preparation (AMP5A) is a novel biologic drug currently under clinical investigation for the treatment of osteoarthritis and the hyperinflammatory response associated with COVID-19. This study aims to elucidate AMP5A effects following the activation of immune cells with agonists of Toll-like receptor (TLR) 7 and/or 8, which detect ssRNA viral sequences. Methods CXCL10 ELISAs were used to evaluate the dynamics of myeloid cells activated with CL075 and CL307, agonists of TLR7/8 and TLR7, respectively. In addition, enrichment analysis of gene sets generated by ELISA arrays was utilized to gain insight into the biologic processes underlying the identified differentially expressed cytokine profiles. Finally, relative potency (REP) was employed to confirm the involvement of mechanisms of action paramount to AMP5A activity. Results AMP5A inhibits the release of CXCL10 from both CL075- and CL307-activated PMA-differentiated THP-1 and peripheral blood mononuclear cells. Furthermore, AMP5A suppresses a distinct set of pro-inflammatory cytokines (including IL-1β, IL-6, IL-12, and CXCL10) associated with COVID-19 and pro-inflammatory NF-κB activation. REP experiments using antagonists specific for the immunomodulatory transcription factors, peroxisome proliferator-activated receptor γ, and aryl hydrocarbon receptor, also indicate that these pathways are involved in the ability of AMP5A to inhibit CXCL10 release. Conclusion Due to the biphasic course of COVID-19, therapeutic approaches that augment antiviral immunity may be more beneficial early in infection, whereas later interventions should focus on inflammation suppression. In this study, we show that AMP5A inhibits TLR 7/8 signaling in myeloid cells, resulting in a decrease in inflammatory mediators associated with hyperinflammation and autoimmunity. Furthermore, data demonstrating that AMP5A activates immunomodulatory transcription factors found to be protective in lung disease is provided. These findings suggest that the modes and mechanisms of action of AMP5A are well suited to treat conditions involving dysregulated TLR 7/8 activation. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

AMP5A modulates Toll-like receptors 7 and 8 single-stranded RNA immune responses in PMA-differentiated THP-1 and PBMC

et al. 2022

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Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets

Woodward,

Fromen

2024

Annual Review of Biomedical Engineering

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There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 26 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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A Randomized Controlled Trial to Evaluate the Safety and Efficacy of a Novel Inhaled Biologic Therapeutic in Adults with Respiratory Distress Secondary to COVID-19 Infection

Cited by 2 publications

References 26 publications

AMP5A modulates Toll-like receptors 7 and 8 single-stranded RNA immune responses in PMA-differentiated THP-1 and PBMC

AMP5A modulates Toll-like receptors 7 and 8 single-stranded RNA immune responses in PMA-differentiated THP-1 and PBMC

Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets

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