The present invention relates to methods and compositions for the treatment and prophylaxis of pulmonary arterial hypertension (PAH) in a human subject in need of such treatment, the methods comprising the pulmonary administration to the subject, preferably via inhalation of a composition comprising rapamycin or a prodrug or derivative thereof.

The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein. In various embodiments, the present invention contemplates a kit comprising an agent that increases prostaglandin EP receptor signaling and staurosporine.

The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein. In various embodiments, the present invention contemplates a kit comprising an agent that increases prostaglandin EP receptor signaling and staurosporine.

Methods are provided of identifying a subject having impaired aldehyde dehydrogenase activity; and administering to the subject a compound comprising an isotopicaliy-modified polyunsaturated fatty acid, an isotopicaliy-modified polyunsaturated fatty acid ester, an isotopicaliy-modified polyunsaturated fatty acid thioester, an isotopicaliy-modified polyunsaturated fatty acid amide, a polyunsaturated fatty acid mimetic, or an isotopicaliy-modified polyunsaturated fatty acid pro-drug, the compound having an isotopic modification that reduces oxidation of the compound, thereby reducing production in the subject of substrate for aldehyde dehydrogenase. Some aspects provide coadministering an isotopicaliy-modified polyunsaturated fatty acid and an oxylipin.

Methods are provided of identifying a subject having impaired aldehyde dehydrogenase activity; and administering to the subject a compound comprising an isotopicaliy-modified polyunsaturated fatty acid, an isotopicaliy-modified polyunsaturated fatty acid ester, an isotopicaliy-modified polyunsaturated fatty acid thioester, an isotopicaliy-modified polyunsaturated fatty acid amide, a polyunsaturated fatty acid mimetic, or an isotopicaliy-modified polyunsaturated fatty acid pro-drug, the compound having an isotopic modification that reduces oxidation of the compound, thereby reducing production in the subject of substrate for aldehyde dehydrogenase. Some aspects provide coadministering an isotopicaliy-modified polyunsaturated fatty acid and an oxylipin.

Methods are provided of identifying a subject having impaired aldehyde dehydrogenase activity; and administering to the subject a compound comprising an isotopicaliy-modified polyunsaturated fatty acid, an isotopicaliy-modified polyunsaturated fatty acid ester, an isotopicaliy-modified polyunsaturated fatty acid thioester, an isotopicaliy-modified polyunsaturated fatty acid amide, a polyunsaturated fatty acid mimetic, or an isotopicaliy-modified polyunsaturated fatty acid pro-drug, the compound having an isotopic modification that reduces oxidation of the compound, thereby reducing production in the subject of substrate for aldehyde dehydrogenase. Some aspects provide coadministering an isotopicaliy-modified polyunsaturated fatty acid and an oxylipin.

In various embodiments, the present disclosure provides compositions and methods for treating and/or preventing cardiovascular-related diseases in subject in need thereof having triglyceride levels of about 200 mg/dL to about 499 mg/dL, diabetes mellitus, and reduced kidney function.

In various embodiments, the present disclosure provides compositions and methods for treating and/or preventing cardiovascular-related diseases in subject in need thereof having triglyceride levels of about 200 mg/dL to about 499 mg/dL, diabetes mellitus, and reduced kidney function.

The present invention relates to ophthalmic compositions and methods for the treatment of dry eye and other inflammatory ocular conditions. In particular, the present invention relates to a composition comprising an esterified anti-inflammatory lipid mediator, which is an ester of an anti-inflammatory lipid mediator that is a reaction product of the anti-inflammatory lipid mediator and a polyol wherein the majority of the anti-inflammatory lipid mediator is present in an ester form. In this way, the compositions are substantially free of an acid form of the anti-inflammatory lipid mediators. Anti-inflammatory lipid mediators can be selected from the group consisting of polyunsaturated fatty acids (e.g., omega-three and omega-six fatty acids), resolvins or a metabolically stable analog, protectins or a metabolically stable analog, lipoxins or a metabolically stable analog, prostaglandins or a metabolically stable analog, retinoic acids, endocannabinoids, metabolites thereof, and mixtures thereof. This composition can be topically delivered to the ocular surface via a preparation, solution, gel, ointment, and/or strip and/or a contact lens.

The present invention relates to ophthalmic compositions and methods for the treatment of dry eye and other inflammatory ocular conditions. In particular, the present invention relates to a composition comprising an esterified anti-inflammatory lipid mediator, which is an ester of an anti-inflammatory lipid mediator that is a reaction product of the anti-inflammatory lipid mediator and a polyol wherein the majority of the anti-inflammatory lipid mediator is present in an ester form. In this way, the compositions are substantially free of an acid form of the anti-inflammatory lipid mediators. Anti-inflammatory lipid mediators can be selected from the group consisting of polyunsaturated fatty acids (e.g., omega-three and omega-six fatty acids), resolvins or a metabolically stable analog, protectins or a metabolically stable analog, lipoxins or a metabolically stable analog, prostaglandins or a metabolically stable analog, retinoic acids, endocannabinoids, metabolites thereof, and mixtures thereof. This composition can be topically delivered to the ocular surface via a preparation, solution, gel, ointment, and/or strip and/or a contact lens.