The present disclosure relates to bioactive self-assembling peptides, nanofibers and hydrogels for activating human mast cells. The peptides, nanofibers and hydrogels comprise a self-assembling peptide that mediates self-assembly linked to a MrgX2 agonist peptide; for example, (RADA)4 linked to proadrenomedullin-12 (PAMP-12).

A means for treating cardiovascular disease, in particular chronic heart failure, especially in terms of a more specific treatment preventing or minimizing pathological hypertrophic signaling while leaving cardiac contractility largely intact. For this purpose the present invention provides a means for treating cardiovascular disease, in particular chronic heart failure, the means specifically inhibiting or causing inhibition of components of the β1-AR/cAMP pathway generating cAMP resulting from activation of the β1-adrenoceptor on the cardiomyocyte cell crest.

The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c, as chloride salts. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. The chloride salt of TAT-NR2B9c shows improved stability compared with the acetate salt form of prior formulations. Formulations of the chloride salt of TAT-NR2B9c are stable at ambient temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefitting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

The present invention relates to a new therapeutic use of a p75NTR neurotrophin binding protein and related molecules in the treatment of osteoarthritis.

Methods for detecting a prostate cancer in a subject comprise detecting a marker selected from an endosomal associated marker and/or a lysosomal associated marker from the subject.

The present invention encompasses treatments for neurologic disorders with recombinant vims vectors encoding G-protein coupled receptors. In particular, the invention is directed to the treatment of addiction disorders including but not limited to alcohol addiction and opiate addiction.

Ligand-drug conjugates for targeted melanoma therapies are disclosed herein. A ligand is conjugated to a cytotoxic cancer drug through a cleavage linker. The ligand can bind to an overexpressed receptor on a cancer cell, resulting in selectivity. This allows the drug to enter a cancer cell selectively and release the drug within that specific cancer cell. Such therapies provide selectivity to melanoma through a ligand that targets the MC1R receptor, which is highly expressed in 80% of malignant melanomas. The ligand-drug conjugates can be used to deliver a wide range of cytotoxic cancer drugs selective to melanoma cells which may solve the drug resistance problem of melanoma in current therapies.

The invention, in some aspects, relates to polypeptide molecules and their encoding nucleic acid molecules and use of such molecules to target opsins to the soma of cells in which they are expressed. Compositions of the invention may be delivered to cells and subjects and used in methods to modulate electrical activity of cells in which they are expressed, and for treatment of diseases and conditions in subjects.

Disclosed herein are compositions and methods relating to agents that target a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.