Nov. 2nd COVID-19 Drug Repurposing Webinar: Ion Channel Targets of Dexamethasone and Sex Steroid Hormones in Airway Disease
Presenter: Dr. Brian Harvey, Emeritus Professor of Molecular Medicine at the Royal College of Surgeons in Ireland
Key concepts discussed in this webinar will include:
- Background to the clinical use of dexamethasone in treating severe COVID-19
- Novel molecular targets of dexamethasone in treating pulmonary edema in COVID-19
- Molecular mechanisms of inhibitory effects of dexamethasone on ion channels
- Gender disparity in inflammatory lung disease: COVID-19, Asthma and Cystic Fibrosis
- Molecular mechanisms of sexual dimorphism in COVID-19 and CF
- Sex hormone-related targets in COVID-19 and CF
In this webinar we will discuss novel molecular targets of the steroid dexamethasone and the steroid hormone estrogen in airway disease with a focus on Covid-19, asthma and cystic fibrosis.
Dexamethasone is a synthetic steroid commonly used in the treatment of inflammatory airway disease which has found a repurposed use in the clinical management of severe COVID-19 lung disease with great success in reducing mortality. The few clinical studies ascribe the therapeutic effects of dexamethasone to its anti-inflammatory actions, however, this does not explain the steroid action on reducing pulmonary edema per se and other targets may be involved. We have recently shown effects of dexamethasone to reduce secretion across human airway cell lines by inhibiting ion channels and these novel effects of the steroid will be discussed in detail.
A gender disparity has been observed since the first reports of COVID-19 appeared with more men than women suffering severe COVID19 disease and dying from it. The molecular mechanisms for this sexual dimorphism are still unknown although the evidence points to differences in estrogen hormone levels and estrogen receptor expression and their regulation of ACE2 receptor biology, after taking into account patients age and underlying comorbidities. We know that a ‘gender gap’ also exists in other lung diseases such as asthma and cystic fibrosis. Asthma has a higher prevalence in boys than in girls before puberty and a higher prevalence and severity in women than in men in adulthood. A similar trend is seen in cystic fibrosis with girls having an earlier onset of lung disease at puberty with more frequent pulmonary exacerbations and shorter life span than men in adulthood. Because of the complexity of these diseases, no single straightforward mechanism can explain the gender differences found in asthma and cystic fibrosis. In the latter half of the webinar we will focus on the influence of female sex hormones on CF pulmonary outcomes and summarise data from in vitro and in vivo experiments on how estrogen might modify airway clearance, immunity and bacterial infection in the CF airways. The potential for novel steroid hormone-related therapeutic interventions will also be discussed.
(both on-demand and live event registrants will receive a copy of the slides and a link to the recording by Nov. 5th)
About the Presenter:
Dr. Brian Harvey is Emeritus Professor of Molecular Medicine at the Royal College of Surgeons in Ireland. He is also a Principal Investigator in the Ion Channel Group at the Centro di Estudios Cientificos, Chile, and Visiting Research Professor at the Sorbonne University, Paris. Brian holds a PhD in Physiology and Biophysics from the National University of Ireland and a DSc honoris causa from Michigan State University. His main research area is in cell and molecular endocrinology of rapid responses to steroid hormones and their regulation of ion channels on which he has published over 300 papers. He is a Chevalier of the French Order of Merit and Member of the Ordre des Palmes Academiques, and an elected fellow of the European Academy of Sciences and the Royal Irish Academy.