The invention provides a combination treatment for ischemia conditions in or otherwise affecting the CNS, such as stroke. The treatment involves administration of a PSD-95 inhibitor and performing reperfusion therapy (e.g., by administration of tPA). Administering a PSD-95 inhibitor in combination with reperfusion therapy increases the efficacy of the reperfusion therapy and/or slows the decline in efficacy of reperfusion therapy with time after onset of ischemia thus extending the window in which reperfusion therapy can be administered.

The invention provides a combination treatment for ischemia conditions in or otherwise affecting the CNS, such as stroke. The treatment involves administration of a PSD-95 inhibitor and performing reperfusion therapy (e.g., by administration of tPA). Administering a PSD-95 inhibitor in combination with reperfusion therapy increases the efficacy of the reperfusion therapy and/or slows the decline in efficacy of reperfusion therapy with time after onset of ischemia thus extending the window in which reperfusion therapy can be administered.

The present disclosure provides methods and compositions for the treatment of diseases and genetic disorders linked to SLC6A1 loss and/or misfunction. The methods and compositions of the present disclosure comprise rAAV vectors and rAAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for a GAT1 polypeptide.

The present invention provides lyophilized formulations of active agents, particularly of TAT-NR2B9c. TAT-NR2B9c has shown promise for treating stroke, aneurysm, subarachnoid hemorrhage and other neurological or neurotraumatic conditions. Such formulations are stable at room temperature thus facilitating maintenance of supplies of such a formulation in ambulances for administration at the scene of illness or accident or in transit to a hospital.

In some embodiments, methods of stimulating fluid intake in a subject in need thereof are described. The methods can comprise stimulating a nitric oxide synthase (nNOS)-positive neuron of the median preoptic nucleus (MnPO). In some embodiments, methods of inhibiting fluid intake in a subject in need thereof are described. The methods can comprise inhibiting stimulation of an nNOS-positive neuron of the MnPO.

Described herein are methods of treating or preventing a fungal infection by administering one or more compounds of the present invention to a subject. The methods of the present invention treat or prevent a fungal infection of C. neoformans, C. gattii, L. prolificans, C. albicans, or a combination thereof, as examples. The compounds of the present invention may be administered to a subject with other agents such as antifungal agents.

During development, OPCs migrate extensively throughout the spinal cord, but their migration is restricted at transition zones (TZ). At these specialized locations, unique glial cells in both zebrafish and mice are at least partially responsible for preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. In order to elucidate the signals that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (AR) causes ectopic OPC migration out of the spinal cord. In our studies, we provide in vivo evidence that endogenous neuromodulation by adenosine regulates OPC migration along motor axons, specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease.

Disclosed herein are compounds, of the class of amine-bearing heterocycles, which act as positive allosteric modulators and silent allosteric modulators of the mu opioid receptor. These compounds are useful for the treatment of pain, drug addiction, and other CNS derived maladies that are controlled directly or indirectly by activation of the mu opioid receptor. Methods for making and using the allosteric modulators disclosed herein are also provided.

Disclosed herein are compounds, of the class of amine-bearing heterocycles, which act as positive allosteric modulators and silent allosteric modulators of the mu opioid receptor. These compounds are useful for the treatment of pain, drug addiction, and other CNS derived maladies that are controlled directly or indirectly by activation of the mu opioid receptor. Methods for making and using the allosteric modulators disclosed herein are also provided.

The invention relates to methods for the treatment and/or prevention of pain, excessive neuronal activity, or epilepsy, and to gene therapy vectors. In particular, the method comprises the overexpression of a CASPR2 polypeptide in sensory neurons of the individual and the gene therapy vector comprises a polynucleotide sequence that encodes a CASPR2 polypeptide or a variant thereof.