This document provides butyrylcholinesterases having an enhanced ability to hydrolyze acyl ghrelin as well as nucleic acids encoding such butyrylcholinesterases. This document also provides methods and materials for treating obesity and/or aggression. For example, methods for administering a nucleic acid encoding a wild-type or mutant butyrylcholinesterase having the ability to hydrolyze acyl ghrelin to a mammal under conditions wherein the level of acyl ghrelin within the mammal is reduced, under conditions wherein the rate of body weight gain of the mammal is reduced, under conditions wherein the mammal’s level of aggression is reduced, and/or under conditions wherein the mammal’s rate of developing stress-induced tissue damage are provided.

Provided is a pharmaceutical composition for treating a degenerative brain disease, including a glycine transporter as an active ingredient. A composition including, as an active ingredient, a glycine transporter protein, a fragment thereof or a nucleic acid molecule encoding the protein or the fragment thereof, a vector including the nucleic acid molecule, or a cell transformed with the vector including the nucleic acid molecule, according to an embodiment, not only can achieve excellent effect(s) of inhibiting amyloid-beta aggregation and/or degrading aggregated amyloid-beta, but also degrades tau protein (and/or inhibition of the aggregation thereof), inhibits the hyperphosphorylation of tau protein, and has excellent blood-brain barrier permeability, thus making it possible to successively act on brain tissues. Therefore, the composition can be effectively applied to the prevention and/or treatment of various degenerative brain diseases associated with amyloid-beta aggregation, tau protein aggregation, and/or hyperphosphorylated tau protein.

Provided is a pharmaceutical composition for treating a degenerative brain disease, including a glycine transporter as an active ingredient. A composition including, as an active ingredient, a glycine transporter protein, a fragment thereof or a nucleic acid molecule encoding the protein or the fragment thereof, a vector including the nucleic acid molecule, or a cell transformed with the vector including the nucleic acid molecule, according to an embodiment, not only can achieve excellent effect(s) of inhibiting amyloid-beta aggregation and/or degrading aggregated amyloid-beta, but also degrades tau protein (and/or inhibition of the aggregation thereof), inhibits the hyperphosphorylation of tau protein, and has excellent blood-brain barrier permeability, thus making it possible to successively act on brain tissues. Therefore, the composition can be effectively applied to the prevention and/or treatment of various degenerative brain diseases associated with amyloid-beta aggregation, tau protein aggregation, and/or hyperphosphorylated tau protein.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

The present invention relates to the use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin for modulating cellular redox homeostasis. A particularly preferred use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin in the context of the present invention is as an antioxidant. The present invention also concerns a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions in subjects suffering from an Usher syndrome. More precisely, this gene therapy takes advantage of an AAV2/8 vector expressing at least one USH1 gene product, preferably SANS.

The present invention relates to the use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin for modulating cellular redox homeostasis. A particularly preferred use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin in the context of the present invention is as an antioxidant. The present invention also concerns a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions in subjects suffering from an Usher syndrome. More precisely, this gene therapy takes advantage of an AAV2/8 vector expressing at least one USH1 gene product, preferably SANS.

The present invention relates to the prevention and/or treatment of retinal disorders, such as cone dystrophies, cone-rod dystrophies, in particular Achromatopsia.

The present invention relates to the prevention and/or treatment of retinal disorders, such as cone dystrophies, cone-rod dystrophies, in particular Achromatopsia.

The present disclosure provides recombinant adeno-associated virus virions with variant capsid protein, where the recombinant AAV (rAAV) virions exhibit one or more of increased ability to cross neuronal cell barriers, increased infectivity of a neural stem cell, increased infectivity of a neuronal cell, and reduced susceptibility to antibody neutralization, compared to a control AAV, and where the rAAV virions comprise a heterologous nucleic acid. The present disclosure provides methods of delivering a gene product to a neural stem cell or a neuronal cell in an individual. The present disclosure also provides methods of modifying a target nucleic acid present in a neural stem cell or neuronal cell.