The disclosure provides epigenetic based approaches and methods using genome editing constructs comprising a zinc finger fused with a repressor domain and/or a dCas9 fused with a repressor domain to treat and manage pain in subjects in need of treatment thereof.

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.

Disclosed are methods of administering AAV viral-based vector compositions useful in delivering a variety of nucleic acid segments and compositions comprising an agent, such as an immunosuppressive agent. Methods and compositions comprising a combination therapy are provided. The disclosed AAV vector compositions include those encoding therapeutic polypeptides to selected mammalian host cells for use in therapeutic autoimmune modalities, including, for example, the in vivo induction of immunological tolerance via a liver-directed AAV -based gene therapeutic regimen for treating and/or ameliorating autoimmune disorders such as multiple sclerosis. The compositions comprising an agent may comprise a sphingosine analog, a glucococorticoid, an mTOR inhibitor, and/or a targeted biologic.

The disclosure concerns compositions and methods for treatment of encephalopathies, including encephalopathies caused by, or associated with, and STXBP1 haploinsufficiency or mutation. Compositions and methods provided herein encompass AAV particles that induce expression of STXBP1, including inducing the expression of STXBP1 in central and/or peripheral nervous system cells.

[Problem] The objectives of the present invention are to provide a method for making an animal that has been stressed, in particular, chronically stressed, affect or develop a specific disease or symptom, and, through elucidating the process from loading stress to affection or onset of the disease or symptom, to provide a useful tool for research and development of preventing or treating methods of the disease or symptom. [Solution] The present invention relates to a method for producing a disease modeling non-human animal having cerebrovascular inflammation, the disease modeling non-human animal, a method for screening a drug using the disease modeling non-human animal, a method for determining the risk of a disease using the presence of cerebrovascular inflammation as an indicator, and a pharmaceutical for preventing and/or treating progressive multiple sclerosis or the like. The present invention enables developing pharmaceuticals for the above described diseases or the like and performing researches for elucidating their pathogenic mechanisms. The present invention also enables determining the risk of affection or onset of progressive multiple sclerosis or the like and preventing and/or treating progressive multiple sclerosis or the like.

The invention provides a method of modulating electrophysiological activity of an excitable cell. The method involves causing exogenous expression of a glycine receptor (GlyR) protein in an excitable cell of a subject. Thereafter, the excitable cell is exposed to an allosteric modulator of the GlyR protein. Modulation of the exogenous GlyR protein (an ion channel) in response to the allosteric modulator modulates the electrophysiological activity of the excitable cell. The method can be used to control pain in a subject. The invention further provides a replication-defective HSV vector comprising an expression cassette encoding a GlyR protein, stocks and pharmaceutical compositions containing such vectors, and a transgenic animal.

Provided herein, in some embodiments, are methods for modulating expression and/or activity of transient receptor potential cation channel subfamily C, member 3 (TRPC3), as well as methods of treating Alzheimer's disease.

The application of PDCD4 as a drug treatment target for anti-depression and/or anti-anxiety disorders has been proved by experimental research that the increase of PDCD4 is an important factor leading to depression in the process of stress; PDCD4 as a target to inhibit its expression or function can play a good antidepressant role, and has no effect on normal physiological state. Therefore, PDCD4 can be used as a target in the preparation and screening of antidepressant and/or anxiolytic drugs, which has a broad application prospect.

What is provided is a fusion protein including any one of proteins of (A) to (C) below; and a tag protein that dimerizes or multimerizes in response to a stimulus, (A) a protein that consists of an amino acid sequence represented by SEQ ID NO: 1; (B) a protein that consists of an amino acid sequence having 70% or more identity with the amino acid sequence represented by SEQ ID NO: 1 and has an aggregate-forming ability, and (C) a protein that consists of an amino acid sequence obtained by performing deletion, substitution, insertion, or addition of one or several amino acids with respect to the amino acid sequence represented by SEQ ID NO: 1 and has the aggregate-forming ability.

Products and methods for assessing the predisposition of a subject to develop an injury-induced chronic mechanical pain and/or an inflammatory-induced chronic thermal pain are provided. More specifically, methods for the assessment of the predisposition of a subject to develop an injury-induced chronic mechanical pain and/or an inflammatory-induced chronic thermal pain using the MYO1A gene as a biomarker and methods of treating selected subjects are provided.