The disclosure relates to methods of treating or reducing ocular pain in a subject. The method includes stimulating nasal tissue in a subject in need of treatment. Optionally, the method can be performed using a stimulator probe having first and second nasal insertion prongs having respective electrodes that can be positioned adjacent to a septum of the subject. The stimulator probe can be connected to a stimulator body having a control subsystem to control an electrical stimulus to be delivered to the subject via the stimulator probe. Optionally, the subject does not have low tear volume.

Disclosed are liquid pharmaceutical compositions including topiramate or a pharmaceutically acceptable salt thereof, meglumine, and a pharmaceutically acceptable excipient. The liquid pharmaceutical composition may further include, e.g., levetiracetam or brivaracetam and/or atorvastatin or a pharmaceutically acceptable salt thereof (e.g., atorvastatin sodium).

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The methods and compositions described herein improve cardiovascular outcomes using measures related to systemic chronic inflammation (the inflammatory age—iAge, the cardiovascular age—cAge, and levels of certain markers) to stratify patients into low risk and high risk groups. The personalized immune proteome signature creates an individualized initial therapy to reduce cAge and to convert high risk patients into low risk patients. High risk patients can be converted to low risk patients by treating the patients to reduce their cAge, iAge and/or improve their CRS.

Methods and compositions for treating symptoms of conditions such as but not limited to osteoarthritis and rheumatoid arthritis. The methods may feature direct intraarticular injection of a recombinant self-complementary adeno-associated virus (sc-rAAV) with a vector adapted to express a modified IL-1Ra peptide. The methods of the present invention may express a therapeutically effective amount of the modified IL-1Ra peptide so as to ameliorating symptoms associated with the condition being treated.

Described herein is a method for treating or prophylaxis of adverse immune reaction to metal debris, metal induced delayed type hypersensitivity (DTH), or inflammatory osteolysis by attenuating the inflammatory response. In one aspect, the method involves inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome/caspase-1 pathway or neutralizing or blocking the activity of interleukin 17 (IL-17), IL-17 receptor (IL-17R), IL-1R, IL-1β, IL-18, IL-21, IL-23 with anti-IL-17, anti-IL-17A, anti-IL-17F, anti-IL-17A/F, anti-IL-1, anti-IL-1β, anti-IL-18, anti-IL-21, anti-IL-23, anti-IL-1R, soluble IL-17 receptors, soluble IL-1 receptors, soluble IL-18 receptors, soluble IL-21 receptors, IL-17 receptor inhibitors, IL-1 receptor inhibitors, IL-18 receptor inhibitors, IL-21 receptor inhibitors, IL-23 receptor inhibitors, blocking agents, inflammasome inhibitors, or combinations thereof.

Described herein is a method for treating or prophylaxis of adverse immune reaction to metal debris, metal induced delayed type hypersensitivity (DTH), or inflammatory osteolysis by attenuating the inflammatory response. In one aspect, the method involves inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome/caspase-1 pathway or neutralizing or blocking the activity of interleukin 17 (IL-17), IL-17 receptor (IL-17R), IL-1R, IL-1β, IL-18, IL-21, IL-23 with anti-IL-17, anti-IL-17A, anti-IL-17F, anti-IL-17A/F, anti-IL-1, anti-IL-1β, anti-IL-18, anti-IL-21, anti-IL-23, anti-IL-1R, soluble IL-17 receptors, soluble IL-1 receptors, soluble IL-18 receptors, soluble IL-21 receptors, IL-17 receptor inhibitors, IL-1 receptor inhibitors, IL-18 receptor inhibitors, IL-21 receptor inhibitors, IL-23 receptor inhibitors, blocking agents, inflammasome inhibitors, or combinations thereof.

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

The present invention relates to compositions comprising anakinra, buffer, and optionally at least one osmolyte and optionally further excipients. Further, the present invention relates to use of said compositions for treatment of for example ophthalmic disorders.