Long-acting agonistic analogs for CLR/RAMP receptors are provided that have an extended half-live in vivo. The agonists are delivered to an individual at a dose sufficient to reduce hypertension and ischemic injury, and to reduce cardiotoxicity associated with chemotherapeutic agents.

Long-acting agonistic analogs for CLR/RAMP receptors are provided that have an extended half-live in vivo. The agonists are delivered to an individual at a dose sufficient to reduce hypertension and ischemic injury, and to reduce cardiotoxicity associated with chemotherapeutic agents.

A multi-arm, degradable polyethylene glycol derivative with a high molecular weight that does not cause vacuolation of cells is provided. A degradable polyethylene glycol derivative represented by the following formula (1):

##STR00001##

wherein n1 and n2 are each independently 45-950, W.sup.1 and W.sup.2 are each independently an oligopeptide of 2-47 residues, a1 and a2 are each independently 1-8, Q is a hydrocarbon chain having 2-12 carbon atoms and optionally containing an oxygen atom and/or a nitrogen atom, X.sup.1 and X.sup.2 are each independently a functional group capable of reacting with a bio-related substance, and L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and L.sup.6 are each independently a divalent spacer.

Methods for treating headache, migraine and related symptoms by administering a CGRP antagonist and a Clostridial derivative are described.

A method for treating, remedying, or preventing inflammatory skin disorders by administering a therapeutically effective dose of at least one an antagonist of a calcitonin gene-related peptide receptor in a pharmaceutically acceptable formulation. The method for treating, remedying, or preventing an inflammatory skin disorder by administering topically and to the prepsoriatic rim a therapeutically effective dose of at least one an antagonist of a calcitonin gene-related peptide receptor in a pharmaceutically acceptable formulation.

Described herein are methods and compositions for treating and/or preventing a microbial infection. Aspects of the invention relate to administering to a subject an agent that inhibits CGRP release and CGRP receptors. In some embodiments of any of the aspects, a subject has been diagnosed with having, or is at risk of having, a microbial infection.

A calcitonin gene-related peptide (CGRP) compound can be selected from N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)-butyrylamino]ethoxy}ethoxy)acetyl][Ser1]alpha-human CGRP peptide (α-CGRP-analogue), or derivatives thereof; or N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]-ethoxy]ethoxy}acetyl][Ser1]beta-human CGRP peptide (β-CGRP-analogue), or derivatives thereof. The CGRP compound can be used to induce myocardial perfusion recovery, in connection with AMI, by activating any CGRP family of receptors with a larger CGRP compound: CGRP potency ratio in the coronary artery than in the mesenteric artery.

The present invention provides novel compositions and methods based on the discovery of the mechanisms and gene expression programs associated with homeostatic ILC2s and proinflammatory ILC2s that drive tissue inflammation. Molecular cues were identified that modulate ILC responses to alarmins using single-cell RNA-sequencing (scRNA-seq) profiles of lung-resident ILCs at steady state and after in vivo stimulation. The neuropeptide CGRP and the CGRP receptor were identified as expressed on ILC2s. Treatment with CGRP reduces allergic lung inflammation and reduces the proliferation and expansion of ILC2 cells. The results demonstrate that CGRP signaling strongly modulates ILC2 responses and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.

The present invention provides new protease-resistant polypeptides, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis.

The present invention provides new protease-resistant polypeptides, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis.