The invention provides methods and materials for treating a seizure disorder such as epilepsy in a patient which employ a vector encoding a modified receptor, the so-called DREADD receptor being characterised by (i) a decreased responsiveness to its endogenous activating ligand (ii) a retained or enhanced responsiveness to an exogenous agonist. The modified receptor is expressed in neurons of a seizure focus in brain of the patient, and an exogenous agonist is administered which activates the modified receptor to reversibly alters the excitability of the neurons in the seizure focus leading to synaptic silencing or other inhibition.

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 a method for modulating pain in a subject comprising activating an exogenous receptor expressed in a target neuron with an effective amount of an agent that specifically activates the exogenous receptor. The present disclosure provides a method for modulating the activity of a neuron comprising activating an exogenous receptor expressed in the neuron by contacting the neuron with an agent that specifically activates the exogenous receptor. The present disclosure provides a method of screening to identify compounds that modulate pain.

The present invention relates to a method for producing cholinergic neurons comprising obtaining neural progenitor cells from stem cells so as to continuously produce cholinergic neural cells with high purity and the same traits, followed by differentiating the neural progenitor cells into the cholinergic neurons, and cholinergic neurons produced therefrom. Since the method of preparing the cholinergic neurons provided in the present invention enables not only production of the cholinergic neurons with high purity, but also rapid production of the cholinergic neurons with the same traits, it can be widely used for effectively treating degenerative cranial nerve diseases such as Alzheimer's disease.

The present invention relates to combinations comprising a positive allosteric modulator (PAM) of metabotropic glutamatergic receptor subtype 2 (mGluR2) or a pharmaceutically acceptable salt or a solvate thereof, or an orthosteric agonist of metabotropic glutamatergic receptor subtype 2 compound or a pharmaceutically acceptable salt or a solvate thereof, and a synaptic vesicle protein 2A (SV2A) ligand.

Methods and compositions for treating a seizure disorder are provided which include administering to the patient a vector encoding a modified receptor for delivery of the modified receptor to the target location, the modified receptor being modified to be activated by a synthetic ligand, wherein the modified receptor inhibits neuronal firing when activated; and administering to the patient the synthetic ligand. Also provided are methods and compositions for treating a seizure disorder in a patient in need thereof by administering to the patient a vector encoding a modified receptor for delivery of the modified receptor to the target location, the modified receptor being modified to be activated by a synthetic ligand, wherein the modified receptor increases neuronal firing when activated; and administering to the patient the synthetic ligand. The methods are used to improve or alleviate one or more symptoms of a seizure disorder.

Disclosed herein are compounds which act as positive allosteric modulators and silent allosteric modulators of the mu opioid receptor. Methods for making and using the allosteric modulators disclosed herein are also provided.

Disclosed herein are compounds which act as positive allosteric modulators and silent allosteric modulators of the mu opioid receptor. Methods for making and using the allosteric modulators disclosed herein are also provided.

The present invention relates to an N-Methyl-D-aspartate (NMDA) receptor antagonist, for use in the treatment of diseases associated with angiogenesis such as tumor angiogenesis, ocular neovascular disease, Age-related macular degeneration (AMD).