Methods are provided for treating a subject with a pain condition. Aspects of the methods include administering a gene therapy to the subject and/or a therapeutically effective amount of a composition that includes a gene therapy vector. Aspects of the vectors may include a nucleic acid sequence encoding a K-Cl cotransporter 2 (KCC2) polypeptide, including e.g., full-length and modified versions thereof. Methods are also provided for treating a subject by editing an endogenous KCC2 locus of the subject to encode a modified KCC2 polypeptide. Methods of detecting the presence of a pain condition are also provided, including where a pain condition detected in such methods is treated according to the methods described herein. Also provided are compositions, such as compositions including a gene therapy vector, such as a lentiviral vector, that includes a viral backbone nucleic acid comprising a sequence encoding a full-length human KCC2 polypeptide or a nucleic acid sequence encoding a modified KCC2 polypeptide.

Methods are provided for treating a subject with a pain condition. Aspects of the methods include administering a gene therapy to the subject and/or a therapeutically effective amount of a composition that includes a gene therapy vector. Aspects of the vectors may include a nucleic acid sequence encoding a K-Cl cotransporter 2 (KCC2) polypeptide, including e.g., full-length and modified versions thereof. Methods are also provided for treating a subject by editing an endogenous KCC2 locus of the subject to encode a modified KCC2 polypeptide. Methods of detecting the presence of a pain condition are also provided, including where a pain condition detected in such methods is treated according to the methods described herein. Also provided are compositions, such as compositions including a gene therapy vector, such as a lentiviral vector, that includes a viral backbone nucleic acid comprising a sequence encoding a full-length human KCC2 polypeptide or a nucleic acid sequence encoding a modified KCC2 polypeptide.

There is disclosed herein a composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhoea, chronic idiopathic nausea, IBD-associated constipation and diarrhoea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux esophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, MS, Alzheimer's Disease, Motor Neuron Disease or autism, the composition comprising: (i) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (ii) at least one anti-clostridial agent selected from the above combined with an opioid blocking agent. There is also disclosed herein a method of treating various gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhoea, chronic idiopathic nausea, IBD-associated constipation and diarrhoea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, MS, Alzheimer's Disease, Motor Neuron Disease or autism, the method comprising administering orally, via enema or by suppository: (i) a composition of the invention; (ii) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (iii) at least one anti-clostridial agent selected from the above and an opioid blocking agent to a patient in need of such treatment.

The present disclosure provides a method of preventing or treating Rett syndrome in a subject in need thereof, including administering to the subject an effective amount of Lactobacillus plantarum subsp. plantarum PS128. Also provided is a composition comprising Lactobacillus plantarum subsp. plantarum PS128 and a carrier thereof for use in preventing or treating Rett syndrome in a subject in need thereof.

Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.G are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions. ##STR00001##

A pharmaceutical product containing β2-microglobulin or a functional variant thereof as an active ingredient in the form of liposomes is provided. The product can increase the concentration of β2-microglobulin in the blood, and can also restore a normal HC/β2-microglobulin molar ratio within membrane MHC-I complexes, or prevent a β2-microglobulin deficit from occurring in the MHC-I complexes, of patients suffering from autoimmune diseases. Methods of treating patients with the pharmaceutical product are also presented.

Provided herein are alpha-conotoxin peptide analogs, including alpha-conotoxin peptide analogs that are covalently attached to polyethylene glycol (PEG), and pharmaceutical compositions of such alpha-conotoxin peptide analogs. Also provided herein are methods of treating or preventing a condition conducive to treatment or prevention by inhibition of an α9-containing nicotinic acetylcholine receptor (nAChR) (e.g., the α9α10 subtype of the nAChR) in a subject.

Provided herein are alpha-conotoxin peptide analogs, including alpha-conotoxin peptide analogs that are covalently attached to polyethylene glycol (PEG), and pharmaceutical compositions of such alpha-conotoxin peptide analogs. Also provided herein are methods of treating or preventing a condition conducive to treatment or prevention by inhibition of an α9-containing nicotinic acetylcholine receptor (nAChR) (e.g., the α9α10 subtype of the nAChR) in a subject.

The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c:

##STR00001##

or a pharmaceutically acceptable salt thereof.

The present invention provides compositions comprising PAMAM dendrimers conjugated with one or more biologically active agents, and their use systemically to target activated microglia/macrophages in retina/choroid and generally, inflammatory and/or angiogenic diseases of the eye.