Methods of minimising effects of smoke exposure

A method of alleviating or ameliorating a symptom of obstructive pulmonary disease, associated with or caused by exposure to smoke, in a subject in need thereof, the method comprising administering to the subject in need thereof an antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE), thereby alleviating or ameliorating a symptom of obstructive pulmonary disease, associated with or caused by exposure to smoke in the subject.

Use of an antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE) in the manufacture of a medicament for the treatment or prevention of obstructive pulmonary disease, associated with or caused by exposure to smoke, in a subject in need thereof.

A method or use according to any one of the preceding claims, wherein the AON that promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE) is administered directly to the airway and/or lungs.

A method or use according to any one of the preceding claims, wherein the administration of the AON promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE) in the total respiratory tract, lower respiratory tract or upper respiratory tract.

A method or use according to any one of the preceding claims, wherein the method promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE) in the lower respiratory tract, preferably the lung.

A method or use according to any one of the preceding claims, wherein the antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE) is administered via inhalation.

A method or use according to any one of the preceding claims, wherein the antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE and/or reduces the production of membrane bound RAGE (mRAGE) is administered via intranasal administration.

A method or use according to any one of the preceding claims, wherein the obstructive pulmonary disease is chronic obstructive pulmonary disease (COPD), emphysema, combined pulmonary fibrosis and emphysema (CPFE), bronchitis, respiratory bronchiolitis/respiratory bronchiolitis-interstitial lung disease, bronchiectasis, asthma, lung, tracheal cancer or a smoking-related interstitial lung diseases (SR-ILDs), preferably the chronic obstructive smoking-related interstitial lung diseases (SR-ILDs) is pulmonary Langerhans cell histiocytosis, desquamative interstitial pneumonitis, or acute eosinophilic pneumonia.

The method of any one of claims 1 to 19 wherein AON promotes splicing in the RAGE pre-mRNA resulting in the inclusion of exon 9b and/or skipping of exon 10.

The method of any one of the preceding claims, wherein the smoke is aerosol or particulate matter from one or more of cigarettes, tobacco or marijuana, coal, wood, oil, gas or other biomass fires.

The method of any one of the preceding claims, wherein the smoke is cigarette smoke.

The method of any one of the preceding claims, wherein the cigarette smoke is “second-hand smoke”.

The method of any one of the preceding claims, wherein the smoke is from burnt organic matter, coal dust, smog, exhaust fumes and other industrial pollutants.

The method of any one of the preceding claims, wherein the subject has experienced an acute exposure to smoke.