The University of Massachusetts Amherst

Deciphering the Role of Vitamin E in the Treatment of Refractory Asthma

The Challenge

To treat the growing subset of asthmatic patients who are refractory to inhaled corticosteroid therapy.

The Innovation/Technology

The discovery that over 90% of patients diagnosed with refractory asthma have airway infections which trigger key mediators in the arachidonic acid pathway. Vitamin isotypes have the ability to reduce infectivity of some of the airway infections and directly impact inflammatory mediators.

The Impact

Development of novel therapeutics for treatment of chronic, refractory asthma; Vitamin E as an adjunctive treatment for hard to control asthma and other respiratory inflammation involving arachidonic acid intermediates.

The Solution

Asthma is a chronic inflammatory disease affecting over 300 million people worldwide and has multiple phenotypes and inflammatory triggers. These phenotypes share common inflammatory features, although their specific immunologic pathways may differ mechanistically. As we dissect and better understand these mechanisms at the molecular level, the treatment of patients with asthma can be better tailored to specific phenotypes. The Webley Lab previously confirmed that a significant subset of hard-to-control asthma is mediated by Chlamydia pneumoniae. Tocotrienols, members of the vitamin E family are potent antioxidants that stand out as potential treatment options for at least some of the asthma phenotypes known today because they are known to block specific molecules in the pro-inflammatory arachidonic acid pathway. In addition, tocotrienols were previously shown to inhibit the extent of chlamydial entry and progeny formation.

The Webley lab hypothesize that tocotrienols and in particular, delta-tocotrienols will reduce the infectivity of C. pneumoniae through inhibition of entry and reduction of progeny released. They further hypothesize that delta-tocotrienols will inhibit multiple enzymes in the arachidonic acid pathway thereby reducing airway inflammation. Since patients with refractory asthma are more likely to experience morbidity and mortality from their disease, this new research could lead to new therapeutics

Targeting the mediators and immune cells involved in asthma inflammation not only represent the basis of many current asthma treatments but highlight the potential for development of novel, superior therapeutic agents in the future. Tocotrienols stand out as a potential adjunctive treatment options for at least some of the asthma phenotypes known today. The current study will help in identifying specific targets of tocotrienols in the arachidonic acid pathway and will confirm their impact on infection-induced and chronic refractory asthma.

Publications
Hahn DL, Schure A, Patel K, Childs T, Drizik E, Webley W. Chlamydia pneumoniae-Specific IgE Is Prevalent in Asthma and Is Associated with Disease Severity. World Biomedical Frontiers Allergy. ISSN: 2328-0166. Dec. 2014
Patel KK, Webley WC. Evidence of Infectious Asthma Phenotype: Chlamydia-Induced Allergy and Pathogen-Specific IgE in a Neonatal Mouse Model. PLoS One. 2013 Dec 20;8(12)
Katir K. Patel§, Erica Anderson§, Paul S. Salva and Wilmore C. Webley*. The Prevalence and Identity of Chlamydia-Specific IgE in Children with Asthma and Other Chronic Respiratory Symptoms. Respiratory Research. 2012 Apr; 18;13 (1):32
David L. Hahn MD MS, Allison Schure MS, Katir Patel MS, Tawanna Childs, Eduard Drizik MS, Wilmore Webley PhD. Chlamydia pneumoniae-specific IgE is prevalent in asthma and is associated with disease severity. 2012 Apr; PLosOne. 7 (4): e35945.
Katir K Patel§, Alfin G Vicencio, Zhongfang Du, Kalliope Tsirilakis, Paul S Salva and Wilmore C. Webley*. Infectious Chlamydia pneumoniae is associated with elevated interleukin-8 and airway neutrophilia in children with refractory asthma. Pediatr Infect Dis J. 2010 Dec; 29 (12):1093-8.
Wilmore C. Webley*, Yaphet Tilahun§, Kimberly Lay§, Katir Patel§, Elizabeth S. Stuart, Chester Andrzejewski, Paul S. Salva. Occurrence of Chlamydia trachomatis and Chlamydia pneumoniae in paediatric respiratory infections. The European respiratory journal, 2009. 33(2): p. 360-7.
 
Contact Info

Wilmore Webley
LSL N229
(413) 577-3139
wilmore@microbio.umass.edu