This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNFα antagonist. The NGF antagonist and the TNFα antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNFα antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNFα antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNFα antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNFα antagonist administered alone.

This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNFα antagonist. The NGF antagonist and the TNFα antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNFα antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNFα antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNFα antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNFα antagonist administered alone.

A protease-resistant neurotrophic peptide is provided. A pharmaceutical composition including the protease-resistant neurotrophic peptide in a pharmaceutically acceptable carrier, in combination with optional adjuvants, stabilizers and/or preservatives, is also provided.

Disclosed herein are Nsp-IL10 polypeptides comprising an Nsp polypeptide and an IL10 polypeptide. In some embodiments, Nsp-IL10 polypeptide is capable of activating an NGF signaling pathway, an IL10 signaling pathway, or both. Also disclosed are methods for treating a disease comprising administering an Nsp-IL10 polypeptide. The methods include treating diseases associated with joint inflammation, such as osteoarthritis.

Disclosed herein are Nsp-IL10 polypeptides comprising an Nsp polypeptide and an IL10 polypeptide. In some embodiments, Nsp-IL10 polypeptide is capable of activating an NGF signaling pathway, an IL10 signaling pathway, or both. Also disclosed are methods for treating a disease comprising administering an Nsp-IL10 polypeptide. The methods include treating diseases associated with joint inflammation, such as osteoarthritis.

Disclosed herein are compositions and methods for the treatment of non-otic diseases or conditions with Trk receptor agonist compositions and formulations.

Disclosed herein are compositions and methods for the treatment of non-otic diseases or conditions with Trk receptor agonist compositions and formulations.

Conjugates for delivering an anti-cancer agent to nerve cells are provided. Conjugate compounds of the present disclosure according to certain embodiments include a compound having a protein, peptide or pepetidomimetic that binds selectively to a neurotrophin receptor, an anti-cancer agent and a linker that covalently bonds the anti-cancer agent to the protein, peptide or pepetidomimetic binds selectively to the neurotrophin receptor. Compositions and methods for delivering an anti-cancer agent selectively into nerve cells (e.g., in the treatment of optic pathway glioma) as well as indications such as perineural invasion and skin cancers are also described. Also provided are methods of making the anti-cancer conjugate compounds.

Conjugates for delivering an anti-cancer agent to nerve cells are provided. Conjugate compounds of the present disclosure according to certain embodiments include a compound having a protein, peptide or pepetidomimetic that binds selectively to a neurotrophin receptor, an anti-cancer agent and a linker that covalently bonds the anti-cancer agent to the protein, peptide or pepetidomimetic binds selectively to the neurotrophin receptor. Compositions and methods for delivering an anti-cancer agent selectively into nerve cells (e.g., in the treatment of optic pathway glioma) as well as indications such as perineural invasion and skin cancers are also described. Also provided are methods of making the anti-cancer conjugate compounds.

The present invention relates to a p75NTR neurotrophin binding protein (NBP)-Fc fusion protein comprising a p75NTR(NBP) portion and an immunoglobulin portion. In certain embodiments, the p75NTR(NBP)-Fc fusion protein is for use in the treatment of pain and/or a symptom of pain.