The present invention relates to a polynucleotide comprising an expressible nucleic acid sequence encoding a relaxin family peptide receptor (RXFP) polypeptide for use in treatment and/or prevention of heart failure in a subject. The present invention further relates to a vector comprising the polynucleotide of the present invention for use in treatment and/or prevention of heart failure, as well as to host cells, RXFP agonists, kits and devices related thereto.

The present invention is based upon the observation that inhibition of NPR-C Signaling pathway leads to the development of pulmonary arterial hypertension (PAH). Accordingly, the invention provides a mouse model for PAH, and proposes a method of using synthetic analogs of the NPR-C signaling pathway, specifically synthetic C-type atrial natriuretic factor or intermediates for, or modulators of, the NPR-C signaling pathway as anti-pulmonary vasculopathy agents. Activators of the NPR-C signaling pathway are disclosed to treat or prevent vasculopathy, including but not limited to PAH and other types of pulmonary hypertension, peripheral vascular disease, critical limb ischemia, coronary artery disease, and diabetic vasculopathy.

In some aspects, the disclosure relates to GDF/BMP antagonists and methods of using GDF/BMP antagonists to treat, prevent, or reduce the progression rate and/or severity of pulmonary hypertension (PH), particularly treating, preventing or reducing the progression rate and/or severity of one or more PH-associated complications. The disclosure also provides methods of using a GDF/BMP antagonist to treat, prevent, or reduce the progression rate and/or severity of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, and right ventricular hypertrophy. The disclosure further provides methods of using a GDF/BMP antagonist to reduce right ventricular systolic pressure in a subject in need thereof.

Intranasal administration of proteins, such as insulin and insulin analogues, in particular immunogenic proteins to the upper posterior region of a nasal cavity of a subject, and in particular the olfactory bulb region.

The present embodiments provide compounds and methods for targeting cells expressing GLP-1 receptor.

Nucleic acid constructs, vectors, and recombinant cells harboring the nucleic acid constructs or vectors are disclosed. The nucleic acid constructs include genes encoding a chimeric antigen receptor (CAR) and/or one or more transcription factors, optionally mutated. The transcription factors include those that mediate proinflammatory cytokine expression, e.g., T-bet, STAT1, or STAT4. Methods are disclosed of co-expression of the CAR and the transcription factor in a human or non-human immune cell, preferably human T cells. Also disclosed are methods for using these cells for immunotherapy, e.g., in treating cancer, infection, autoimmunity, allergy or inflammation diseases by the administration of a prophylactically or therapeutically effective amount of one or more of the nucleic acid constructs, vectors, and/or immune cells, e.g., human CAR-T cells, described herein.

Provided herein are methods for the treatment of bone disorders that are associated with kidney disease wherein the methods comprise administration of Activin-ActRIIA inhibitors to a subject in need of the treatment. Also provided herein are methods and compositions for the treatment of low turnover bone disorders wherein the methods comprise administration of Activin-ActRIIA inhibitors to a subject in need of the treatment. Further provided herein are compositions for the treatment of bone disorders that are associated with kidney disease and compositions for the treatment of low turnover bone disorders and vascular calcification.

Methods of treating patients having inflammatory bowel disease (IBD) or primary sclerosing cholangitis (PSC) are provided herein.

The present invention relates to methods for reversing maladaptations involving the corticotropin-releasing factor receptor subtype 2 (CRFR2). It is postulated that in functional somatic syndrome (FSS), a group of diseases with overlapping symptoms, including systemic exertion intolerance disease (SEID, also known as chronic fatigue syndrome or myalgic encephalomyelitis), and several others, this receptor is up-regulated and relocated to the neuronal membranes of key regions of the brain including the raphe nuclei, the limbic system and the cortex. This configuration leads to a dysfunctional stress response. According to one embodiment of the invention, a method for reversing CRFR2 maladaptations includes the sustained stimulation of the receptor over a period of time to bring about a persistent receptor endocytosis, resulting in measurable symptom improvement.

The disclosure relates to long acting parathyroid or parathyroid hormone like fusion polypeptides comprising a receptor polypeptide and its use in the treatment of hypoparathyroidism and osteoporosis.