FOXa2 in the Diagnosis and Treatment of Inflammatory Diseases of the Lung
Background
- Asthma and other chronic obstructive pulmonary diseases (COPD) affect over 12 million Americans and are identified by airflow limits and hyper-repsonsiveness to various stimuli ending in excessive airway narrowing.
- Airway obstructive diseases are distinguished by limited airflow by constriction of airway smooth muscle, edema and hypersecretion of mucus.
- Airway inflammation can be provoked by allergens, cold air, exercise, infections and air pollution with a variety of inflammatory mediators and cell types involved.
- Inflammatory lung diseases are very harmful since they involve obstructed breathing, hypoxia, hypercapnea and lung tissue damage.
- Current therapies include the use of glucocorticoids, beta-agonists, methyl xanthines and NSAIDs.
- While these agents provide short-term beneficial relief of discomfort, they fail to address the underlying inflammatory processes that cause these diseases and are associated with potentially serious side effects such as immunosuppression, liver toxicity, drug-induced lung disease and bone marrow suppression.
Description of Current Technology
The current invention, from the laboratory of Dr. Jeffrey Whitsett, centers around the FOXa2 gene and polypeptide as both a diagnostic and therapeutic tool for asthma and other COPDs. In mice in which the FOXa2 gene is selectively deleted in respiratory epithelial cells, fewer peripheral lung saccules and decreased alveolar septation are observed. These mice also display airway enlargement, focal neutrophil infiltration and goblet cell hyperplasia, all supported by morphometric analysis. Increased numbers of neutrophils and macrophages are observed in bronchoalveolar lavage fluid taken from these mice. Airway and tissues resistance and elastance are significantly increased and compliance decreased, suggesting abnormalities in both conducting airways and alveolar regions. IL-4/IL-13 allergen challenge resulted in a loss of FOXa2 activity via stat-6 dependent pathway and caused airway remodeling, goblet cell hyperplasia and inflammation. More importantly, significant positive correlations have been found in human lung sections obtained at autopsy or at lobectomy from ten patients with chronic lung disease. In all subjects, mucous producing cells lacked FOXa2 expression compared to non-diseased samples of human lung and in nuclei of adjacent, non-goblet epithelial cells. Five of these subjects were infants with bronchopulmonary dysplasia in the first six months after birth. In all subjects Alcian blue reactive, mucus-producing cells lacked FOXa2 staining. Loss of FOXa2 is sufficient to cause goblet cell hyperplasia in the absence of inflammatory stimuli. Thus, FOXa2 plays a key role in the regulation of lung function and in maintaining homeostasis in lung tissue. Absence of this gene or gene product significantly compromises normal lung and may be involved in the etiology of several obstructive pulmonary diseases suggesting FOXa2 gene therapy or gene product may represent a novel approach to the treatment of these diseases. Appropriate patent applications have been filed.
Objective
The Cincinnati Children's Research Foundation is actively seeking a corporate partner as a collaborator on further research with this technology and to be a licensee to ultimately bring novel and appropriate therapies to the public.
Contact
To discuss this opportunity further and/or to receive confidential and proprietary information relating to this technology, please contact:
Joseph D. Fondacaro, PhD
Director, Intellectual Property & Venture Development
Cincinnati Children's Research Foundation
Mail Location 7032
3333 Burnet Avenue
Cincinnati, Ohio 45229-3039
Phone: 513-636-7695
Fax: 513-636-8453
E-mail: jdfonda@cchmc.org
Related Study Information
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