40 results about "Aspartate receptors" patented technology

The present invention relates to a microRNA-based short hairpin RNA for gene silencing the genetic expression of NR1 subunit of N-methyl-D-aspartate receptor comprises a single strand RNA fragment comprising a first fragment, a second fragment and a connecting fragment, wherein the first fragment and the second fragment are complementary to each other, and are spaced and connected by the connecting fragment, with the connecting fragment being randomly arranged nucleotides, with the first fragment having a Drosha recognized cleavage site, a silencing site and a Dicer recognized cleavage site, with the Drosha recognized cleavage site and the Dicer recognized cleavage site being spaced and connected by the silencing site, with the silencing site encoding homologous nucleotides corresponding to NR1 subunit of subcutaneous N-methyl-D-aspartate receptor.

Disclosed are novel compounds of the formulaor a pharmaceutically acceptable salt or solvate thereof, whereinR1, R2, R3, R4 and X are as defined in the specification.Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and / or enhancing stress resilience in a subject. In certain embodiments, an effective amount, of an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, such as ketamine, or a pharmaceutically acceptable salt or derivative thereof, is administered to a subject prior to a stressor.

Disclosed are compounds of the formulaor a pharmaceutically acceptable salt or solvate thereof, whereinR1 isR is —C(O)—N(R27)(R28) orand the remaining variables are as defined in the specification.Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Disclosed are novel compounds of the formulaor a pharmaceutically acceptable salt or solvate thereof, whereinR1, R2, R3, R4 and X are as defined in the specification.Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

The invention relates to a chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR comprises an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system. The invention relates to a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid molecule comprising a sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a sequence encoding a transmembrane domain, and a sequence encoding an intracellular signaling domain. In one embodiment, the autoantigen encoded by the nucleic acid sequence comprises or consists of an N- methyl-D-aspartate receptor (NMDAR), or one or more NMDAR fragments. The invention further relates to the chimeric autoantibody receptor (CAAR) protein of the invention, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR) of the invention, a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and the use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

Multifunctional compounds are provided, comprising two or more functional moieties selected from: (i) a moiety that imparts an iron chelator function; (ii) a moiety that imparts a neuroprotective function; (iii) a moiety that imparts combined antiapoptotic, neuroprotective and / or neurorestorative functions; (iv) a moiety that imparts brain MAO inhibition, preferably with little or no MAO inhibition in liver and small intestine; (v) a moiety that imparts cholinesterase inhibitory function; and (vi) a moiety that imparts an N-methyl-D-aspartic acid receptor (NMDAR) inhibition, and pharmaceutically acceptable salts and optical isomers thereof. The multifunctional compounds are useful in the treatment or prevention of diseases, disorders or conditions that can be prevented and / or treated by iron chelation therapy, and / or neuroprotection and / or neurorestoration, and / or apoptosis inhibition and / or MAO inhibition and / or cholinesterase inhibition and / or NMADR inhibition. The present invention encompasses compounds of the formulas I to VI.

Methods for identifying patients diagnosed with treatment resistant or refractory depression, pain or other clinical indications who are eligible to receive N-methyl-D-aspartate receptor antagonist, glycine receptor beta (GLRB) modulator, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-based therapies to include determining the appropriate medication, an optimal dose for each patient, and determining which patients are not eligible to receive the therapy. The pharmacogenomic clinical decision support assays include targeted single nucleotide polymorphisms and clinical values or a combination of targeted single nucleotide polymorphisms, targeted ketamine- specific expansion and contraction of topologically associated domains, and clinical values. The methods described herein allow for a more effective determination of which patients will experience drug efficacy and which patients will experience adverse drug events. The methods provide personalized patient recommendations for dose, the frequency of medication administration, and recommendations on drug choice.