Uses of antagonists of hyaluronan signaling
Inventors
Garantziotis, Stavros • Hollingsworth, John W. • Toole, Bryan P. • Liu, Jian
Assignees
University of North Carolina at Chapel Hill • MUSC Foundation for Research and Development • Duke University • US Department of Health and Human Services
Publication Number
US-9717752-B2
Publication Date
2017-08-01
Expiration Date
2033-03-08
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Abstract
Described herein is the finding that hyaluronan antagonists that inhibit hyaluronan signaling are capable of inhibiting airway inflammation and airway hyperresponsiveness (AHR). The present disclosure provides a method of preventing or reducing AHR in a subject suffering from or at risk for AHR by administering a hyaluronan antagonist. Also provided is a method of treating an airway disease or disorder in a subject by administering a hyaluronan antagonist. Hyaluronan antagonists include, for example, heparosan and hyaluronan oligosaccharides (oHAs). In some embodiments, the hyaluronan antagonist is administered locally to the airway, such as with an inhaler or nebulizer.
Core Innovation
The invention provides methods of treating airway diseases or disorders, or preventing or reducing airway hyperresponsiveness (AHR), by administering hyaluronan antagonists such as heparosan and hyaluronan oligosaccharides (oHAs). These antagonists inhibit hyaluronan signaling, which leads to a reduction in airway inflammation and airway hyperresponsiveness. The invention includes administering therapeutically effective amounts of these antagonists to subjects suffering from or at risk for AHR, including via local delivery such as aerosol inhalation.
The problem addressed by the invention is the lack of specific, causative, and physiologic treatments for airway hyperresponsiveness. Current treatments for airway diseases like asthma and chronic obstructive pulmonary disease (COPD) are non-specific, often involving bronchodilators and immunosuppressants that have significant side effects, including increased mortality risks and other adverse effects. AHR is a major component of airway disease, presenting with symptoms like wheezing and cough, and existing therapies do not adequately target the molecular pathways underlying AHR.
Claims Coverage
The patent contains one independent claim focused on a method of treating airway diseases or disorders and preventing or reducing airway hyperresponsiveness using heparosan.
Use of heparosan to treat airway diseases or disorders and prevent or reduce airway hyperresponsiveness
The method includes selecting a subject with an acute or chronic airway disease or disorder or at risk for AHR, and administering a therapeutically effective amount of heparosan to treat the disease or prevent or reduce AHR in the subject.
Formulation for local aerosol delivery to the airway
The administered heparosan is formulated for local delivery, including aerosol delivery methods using inhalers (dry powder inhalers or metered-dose inhalers) or nebulizers.
Dosing regimen
Heparosan is administered daily at doses ranging from about 1 to about 100 μg, with particular dosages of about 10 to about 50 μg described as effective.
The independent claim covers the administration of heparosan for therapeutic treatment or prevention of airway diseases and AHR, emphasizing local aerosol delivery via inhalation devices and specified dosing ranges for effective treatment.
Stated Advantages
The invention provides specific inhibition of hyaluronan signaling, which leads to reduced airway inflammation and airway hyperresponsiveness.
Local aerosol delivery allows for administration of smaller doses with equal or greater therapeutic effect and minimal adverse effects compared to systemic treatments.
The methods offer potential for more targeted and physiologic treatment of airway diseases, reducing the side effects associated with current non-specific treatments.
Documented Applications
Treatment of acute or chronic airway diseases or disorders such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, obliterative bronchiolitis, diffuse panbronchiolitis, and cryptogenic organizing pneumonia.
Prevention or reduction of airway hyperresponsiveness triggered by environmental factors (ozone, particulate matter, allergens), chemical triggers (ammonia, toxic chemicals), respiratory infections, exertion, stress, and airway injury from intubation or chemical burns.
Administration of hyaluronan antagonists locally to the airway via aerosol delivery methods including inhalers and nebulizers for direct treatment.
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