Abstract: Provided herein is a gene therapy for neurological disease using a recombinant adeno-associated virus (rAAV) virion as a vector to express an eEF1A2 protein or functional variant thereof. The rAAV virion may use a neuron-specific promoter, e.g., a human synapsin 1 (hSYN) promoter. The capsid may be an AAV9 capsid or functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intracerebrally and/or intravenously of the rAAV virion, and other compositions and methods.

Abstract: The invention provides expression vectors, nucleic acids, vector particles and methods of treatment involving these vector particles, comprising an engineered KCNA1 gene encoding an edited Kv1.1 potassium channel, as well as methods of confirming the presence of engineered KCNA1 mRNA in a cell. The features of the engineered KCNA1 gene combine to advantageously enhance the translation and activity of the Kv1.1 protein and improve detection of KCNA1 gene expression in a cell and can be used for example in the treatment of epilepsy and similar neurological disorders.

Abstract: The invention provides expression vectors or vector systems comprising a polynucleotide sequence encoding a polypeptide, wherein the gene is operably linked to a neuronal activity-dependent promoter suitable to drive expression of the gene product in a subject’s neural cells. The features of the expression vectors combine to advantageously improve the treatment of a neurological disorder associated with neuronal hyperexcitability in a subject. The invention also provides the expression vectors or vector systems for use in related methods of treatment, as well as viral particles, cells, kits and methods using the expression vectors or vector systems.

Abstract: The invention provides expression vectors, nucleic acids, vector particles and methods of treatment involving these vector particles, comprising an engineered KCNA1 gene encoding an edited Kv1.1 potassium channel, as well as methods of confirming the presence of engineered KCNA1 mRNA in a cell. The features of the engineered KCNA1 gene combine to advantageously enhance the translation and activity of the Kv1.1 protein and improve detection of KCNA1 gene expression in a cell and can be used for example in the treatment of epilepsy and similar neurological disorders.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The invention pertains to a human N-type calcium channel isoform, h?1B+SFVG, which is involved in central nervous system signaling, and nucleic acids relating thereto. The present invention also includes fragments and biologically functional variants of the human h?1B+SFVG channel. Also included are human N-type calcium channel h?1B+SFVG subunit inhibitors which inhibit human N-type calcium channel h?1B+SFVG subunit activity by inhibiting the expression or function of human N-type calcium channel h?1B+SFVG subunit. The invention further relates to methods of using such nucleic acids, polypeptides, and inhibitors in the treatment and/or diagnosis of disease, such as in methods for treating stroke, pain, e.g., neuropathic pain, and traumatic brain injury.

Abstract: A method for determining the dosage regime of a drug suitable for use in the treatment of a neurological condition in a subject, which method comprises typing the SCN1A gene of the subject. The method may be used to determine the dosage regime of an anti-epileptic drug (AED) in a subject. A subject may be treated in accordance with the dosage regime determined using such a method.

Abstract: The invention pertains to a human N-type calcium channel isoform, h?1B+SFVG, which is involved in central nervous system signaling, and nucleic acids relating thereto. The present invention also includes fragments and biologically functional variants of the human h?1B+SFVG channel. Also included are human N-type calcium channel h?1B+SFVG subunit inhibitors which inhibit human N-type calcium channel h?1B+SFVG subunit activity by inhibiting the expression or function of human N-type calcium channel h?1B+SFVG subunit. The invention further relates to methods of using such nucleic acids, polypeptides, and inhibitors in the treatment and/or diagnosis of disease, such as in methods for treating stroke, pain, e.g., neuropathic pain, and traumatic brain injury.

Abstract: The invention pertains to a human N-type calcium channel isoform, h?1B+SFVG, which is involved in central nervous system signaling, and nucleic acids relating thereto. The present invention also includes fragments and biologically functional variants of the human h?1B+SFVG channel. Also included are human N-type calcium channel h?1B+SFVG subunit inhibitors which inhibit human N-type calcium channel h?1B+SFVG subunit activity by inhibiting the expression or function of human N-type calcium channel h?1B+SFVG subunit. The invention further relates to methods of using such nucleic acids, polypeptides, and inhibitors in the treatment and/or diagnosis of disease, such as in methods for treating stroke, pain, e.g., neuropathic pain, and traumatic brain injury.

Abstract: The invention pertains to a human N-type calcium channel isoform, h&agr;1B+SFVG, which is involved in central nervous system signaling, and nucleic acids relating thereto. The present invention also includes fragments and biologically functional variants of the human h&agr;1B+sFvGchannel. Also included are human N-type calcium channel h&agr;1B+SFVG subunit inhibitors which inhibit human N-type calcium channel h&agr;1B+SFVG subunit activity by inhibiting the expression or function of human N-type calcium channel h&agr;1B+SFVG subunit. The invention further relates to methods of using such nucleic acids, polypeptides, and inhibitors in the treatment and/or diagnosis of disease, such as in methods for treating stroke, pain, e.g., neuropathic pain, and traumatic brain injury.

Abstract: The invention pertains to a human N-type calcium channel isoform, h&agr;1B+SFVG, which is involved in central nervous system signaling, and nucleic acids relating thereto. The present invention also includes fragments and biologically functional variants of the human h&agr;1B+SFVG channel. Also included are human N-type calcium channel h&agr;1B+SFVG subunit inhibitors which inhibit human N-type calcium channel h&agr;1B+SFVG subunit activity by inhibiting the expression or function of human N-type calcium channel h&agr;1B+SFVG subunit. The invention further relates to methods of using such nucleic acids, polypeptides, and inhibitors in the treatment and/or diagnosis of disease, such as in methods for treating stroke, pain, e.g., neuropathic pain, and traumatic brain injury.