METHODS OF TREATING OR PREVENTING RESPIRATORY CONDITIONS
The present disclosure provides methods of treating or preventing respiratory condition and/or for treating an IgE-mediated allergy and/or for reducing an allergic response to an allergen and/or for inducing anergy to an allergen in a subject and/or improving lung function in a subject suffering from an allergy comprising administering to a subject a population of cells enriched for STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom.
1 . A method of treating or preventing a respiratory condition and/or for treating an IgE-mediated allergy and/or for reducing an allergic response to an allergen and/or for inducing anergy to an allergen in a subject and/or improving lung function in a subject suffering from an allergy, the method comprising administering to the subject a population of cells enriched for STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom.
2 . The method of claim 1 , wherein the respiratory condition is an acute respiratory condition or a chronic respiratory condition.
3 . The method of claim 1 or claim 2 , wherein the respiratory condition is an inflammatory respiratory condition, an obstructive respiratory condition or a restrictive respiratory condition.
4 . The method of claim 3 , wherein the respiratory condition or allergy is an obstructive respiratory condition or allergy or an inflammatory lung condition or allergy.
5 . The method of claim 4 , wherein the respiratory condition is asthma.
6 . The method of claim 5 , wherein the asthma is acute asthma, chronic asthma, severe asthma and/or refractory asthma.
7 . The method of claim 6 , wherein the asthma is long acting beta agonist (LABA) refractory asthma or steroid refractory asthma.
8 . The method of claim 3 , wherein the respiratory condition is a restrictive respiratory condition.
9 . The method of claim 8 , wherein the respiratory condition is idiopathic pulmonary fibrosis.
10 . The method of claim 1 , wherein the condition is allergy to house dust mite allergen (HDM) or the allergen is HDM.
11 . The method of any one of claims 1 to 10 comprising administering a population of cells enriched for STRO-1 bright cells and/or progeny thereof and/or soluble factors derived therefrom.
12 . The method of any one of claims 1 to 11 , wherein the population enriched for STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom are administered systemically.
13 . The method of claim 12 , wherein the population enriched for STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom are administered intravenously or intranasally.
14 . The method of any one of claims 1 to 13 , wherein the population and/or the progeny and/or the soluble factors are administered a plurality of times.
15 . The method of any one of claims 1 to 14 , comprising the subject and administering a further dose of the population and/or the progeny and/or the soluble factors when one or more of the following occurs:
(i) a subject begins to persistently wheeze and/or cough and/or have chest tightness and/or have difficulty breathing;
(ii) a subject shows one or more of the following when assessed by spirometer:
a) 20% difference on at least three days in a week for at least two weeks;
b) ≥20% improvement of peak flow following treatment with:
10 minutes of inhaled β-agonist;
six weeks of inhaled corticosteroid;
14 days of 30 mg prednisolone.
c) ≥20% decrease in peak flow following exposure to a trigger;
(iii) bronchoscopy showing abnormal cells and/or foreign substances and/or blockages in the respiratory tract of a subject; or
(iv) chest CT scan showing abnormalities of the blood vessels in the lungs, accumulation of blood or fluid in the lungs, bronchiectasis, pleural effusion or pneumonia.
16 . The method of any one of claims 1 to 15 comprising administering a dose of the population and/or the progeny and/or the soluble factors sufficient to achieve one or more of the following:
(i) improved bronchial hyperresponsiveness;
(ii) reduced eosinophil infiltration of the lung or bronchoalveolar lavage fluid;
(iii) reduced neutrophil infiltration of the lung or bronchoalveolar lavage fluid;
(iv) reduced late asthmatic response;
(v) reduced early asthmatic response; and/or
(vi) reduced lung remodeling/fibrosis.
17 . The method of any one of claims 1 to 16 comprising administering between 1×10 6 to 150×10 6 STRO-1 + cells and/or progeny thereof.
18 . The method of any one of claims 1 to 17 comprising administering a whole body dose of STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom.
19 . The method of claim 18 comprising administering 150×10 6 STRO-1 + cells and/or progeny thereof in 10 mL to the subject.
20 . The method of any one of claims 1 to 19 , wherein the population enriched for STRO-1 + cells and/or progeny cells are autogeneic or allogeneic and/or the soluble factors are derived from autogeneic or allogeneic cells.
21 . The method of any one of claims 1 to 20 , wherein the population enriched for STRO-1 + cells and/or progeny cells have been culture expanded prior to administration and/or prior to obtaining the soluble factors.
22 . The method of any one of claims 1 to 21 , wherein the population enriched for STRO-1 + cells are STRO-1 bri , and/or express tissue non-specific alkaline phosphatase (TNAP) and/or the progeny cells and/or soluble factors are derived from STRO-1 + cells that are STRO-1 bri and/or express TNAP.
23 . The method according to any one of claims 1 to 22 , wherein the STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom are administered in the form of a composition comprising said STRO-1 + cells and/or progeny cells thereof and/or soluble factors derived therefrom and a carrier and/or excipient.
24 . A population of cells enriched for STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom for use in the treatment or prevention of a respiratory condition and/or for treating an IgE-mediated allergy and/or for reducing an allergic response to an allergen and/or for inducing anergy to an allergen and/or improving lung function in a subject suffering from an allergy.
25 . Use of a population of cells enriched for STRO-1 + cells and/or progeny thereof and/or soluble factors derived therefrom in the manufacture of a medicament for treating or preventing a respiratory condition in a subject and/or for treating an IgE-mediated allergy and/or for reducing an allergic response to an allergen and/or for inducing anergy to an allergen and/or improving lung function in a subject suffering from an allergy.