Methods for treating inflammatory conditions of the lungs
AssigneeDefensin Therapeutics ApS
InventorsPeter Nordkild, Søren Kjærulff
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Abstract
The present invention relates to methods for treatment or prevention of asthma, mild intermittent asthma, mild persistent asthma, moderate persistent asthma, severe persistent asthma, eosinophilic asthma, neutrophilic asthma, steroid refractory asthma, status asthmaticus, pneumonia, bronchiectasis, COPD, sarcoidosis, and lung cancer based on reducing airway hyper responsiveness, increasing pulmonary compliance, reducing lung inflammation, reducing inflammatory cell count in bronchoalveolar fluid and reducing cytokine production by administration of a mammalian α- and/or β-defensin.
Claims28
A method of treatment and/or prevention of inflammatory diseases of the respiratory system the method comprising oral or intrapulmonary administration of at least one defensin preferably wherein the subject suffers from asthma.
The method of any of the preceding claims, comprising reducing histological lung inflammation, inflammatory cell count in bronchoalveolar lavage fluid, rebalancing the immune system with normalization of inflammatory cytokine production in lung tissue homogenates and prevention/treatment of a cytokine storm.
The method of any of the preceding claims comprising increasing pulmonary compliance, in reducing airway hyper responsivenes, and/or in increasing the peak expiratory flow in a subject in need thereof.
The method of any of the preceding claims, comprising increasing gene richness, the number of phylae, increasing butyrate production and/or tryptophan production, decreasing acetate production of and/or from lung microbiota.
The method of any of the preceding claims, comprising maintaining and/or stabilizing a normal microbiota in the lung.
The method of any of the preceding claims, comprising increasing forced expiratory volume at 1 second (FEV1) and/or peak expiratory flow rate PEFR, or reducing PEFR variability.
The method according to any one of preceding claims, wherein said defensin is selected from a group consisting of HD5, HD6, hBD-1, hBD-2, truncated hBD2, hBD-3 and hBD-4.
The method according to any one of preceding claims, wherein said polypeptide is comprised in a composition, wherein said composition comprises more than one defensin, such as two defensins, such as three defensins.
The method according to 10, wherein said two defensins are hBD-2 and HD5.
The method according to any one of preceding claims, wherein said defensin further comprises at least one additional moiety selected from a group consisting of a cell penetrating peptide (CPP), an Albumin Binding Moiety (ABM), a detectable moiety (Z), and a half-life extending peptide.
The method according to any one of the preceding claims, wherein the subject has asthmatic symptoms>2 times per week, such as daily symptoms, such as continuous symptoms.
The method according to any one of the preceding claims, wherein the subject has asthmatic attacks of varying intensity, such as attacks affecting activity, such as attacks limiting physical activity.
The method according to any one of the preceding claims, wherein the subject has asthmatic symptoms at night>2 times per month, such as >2 times a week that may last for days, such as frequent night time symptoms.
The method according to any one of the preceding claims, wherein the subject has a forced expiratory volume at 1 second (FEV1)<80%, such as a FEV1 of 60-80%, such as a FEV1<60%.
The method according to any one of the preceding claims, wherein the subject has a peak expiratory flow rate PEFR with a variability of >20%, such as PEFR variability of 20-30%, such as a PEFR variability>30%, such as a PEFR variability>60%.
The method according to any one of the preceding claims, wherein the defensin is administered in combination with glucocorticoids, β-agonists, leukotriene receptor antagonists, theophylline, antibiotics, rifaximin, immunosuppressants, chemo- or immune therapy, prebiotics, probiotics, tryptophane, short chain fatty acids, HNP-1, HNP-2, HNP-3, HNP-4, cathelicidin, lactoferrin, lactoferricin, lysozyme, fecal transplants or any combination thereof.
The method according to any one of the preceding claims, wherein the daily dosage is between 0.1 and 10 mg defensin/kg, such as between 0.5 and 5 mg defensin/kg, such as between 1 and 2 mg defensin/kg per day, such as 1.2 mg defensin/kg per day.
The method according to any one of the preceding claims, wherein said defensin is administered at least one time a day, such as at least twice a day, such as at least three times a day, such as at least four times a day, such as five times a day or continuously.
The method according to any one of the preceding claims, wherein said intrapulmonary administration is intratracheal, intrabroncial, or bronchio-alveolar.
The method according to any one of the preceding claims, wherein said intrapulmonary administration is by an inhaler, nebulizer, or vaporizer.
The method according to any of the preceding claims, wherein said lung cancer is small cell lung cancer or non-small cell lung cancer, optionally wherein said cancer is being treated by radiation therapy, by chemotherapy and/or surgery.
A defensin polypeptide for use in a method of treatment according to any of the preceding claims.
Use of a defensin polypeptide for the preparation of a medicament for the treatment of a disorder as defined in any of the preceding claims.
Dependencies are inferred from the claim text.