The Scripps Research Institute

Scripps Clinic and Research Foundation

Modgene, LLC

Hilbush, Brian S.

Sutcliffe, J. Gregor

J Gregor Sutcliffe

Mark G Erlander

Luis De Lecea

Karl W Hasel

Steven J Henriksen

Brian S Hilbush

George R Siggins

Frank H Burton

Timothy W Lovenberg

Kaare M Gautvik

Floyd E Bloom

Patria E Danielson

Vigdis T Gautvik

Thomas S Kilduff

Pamela E Foye

The present invention relates to methods and compositions for modulating levels of amyloid-&#x3b2; peptide (A&#x3b2;) exhibited by non-neuronal (i.e., peripheral) cells, fluids, or tissues. The invention also relates to modulation of A&#x3b2; levels via selective modulation (e.g., inhibition) of &#x3b3;-secretase activity. The invention also relates to methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an A&#x3b2;-related disorder, by administering a compound that results in the modulation of &#x3b3;-secretase in a non-neuronal tissue, either directly or indirectly to prevent, treat or ameliorate the symptoms of a brain A&#x3b2; disorder, such as Alzheimer's disease.

Compositions and methods for reduction of amyloid-beta load

The present invention relates generally to nucleic acids encoding a novel neuropeptide designated cortistatin. The cortistatin nucleic acids, proteins and polypeptides thereof along with anti-cortistatin antibodies are useful in both screening methods, diagnostic methods and therapeutic methods related to modulation of sleep and disorders thereof.

Antibodies to cortistatin: neuropeptides, compositions and methods

Disclosed are hypocretin polynucleotides and hypocretin polypeplides, as well as antibodies, oligonucleotides, diagnostic kits and methods, and therapeutic compositions and methods. Hypocretin, one of several novel liypothalamic-specific polypeptides identified isolated and sequenced, is localized to regions of the hypothalamus involved in appetite and feeding behavior. Hypocretin polypeptides are biologically active, producing electrical changes in neurons, lowering body temperature and reducing food intake.

Hypothalamus-specific polypeptides

An improved method for the simultaneous sequence-specific identification of mRNAs in a mRNA population allows the visualization of nearly every mRNA expressed by a tissue as a distinct band on a gel whose intensity corresponds roughly to the concentration of the mRNA. In general, the method comprises the formation of cDNA using anchor primers to fix a 3&prime;-endpoint, producing cloned inserts from the cDNA in a vector containing a bacteriophage-specific promoter for subsequent RNA synthesis, generating linearized fragments of the cloned inserts, preparing cRNA, transcribing cDNA from the cRNA using a set of 5&prime;-RT primers, and performing PCR using a 3&prime;-PCR primer whose sequence is derived from the vector and a set of 5&prime;-PCR primers that is derived from the 5&prime;-RT primers used for transcription of cDNA from cRNA. The method can identify changes in expression of mRNA associated with the administration of drugs or with physiological or pathological conditions.

Method for simultaneous identification of differentially expressed mRNAs and measurement of relative concentrations

An improved method for the simultaneous sequence-specific identification of mRNAs in a mRNA population allows the visualization of nearly every mRNA expressed by a tissue as a distinct band on a gel whose intensity corresponds roughly to the concentration of the mRNA. In general, the method comprises the formation of cDNA using anchor primers to fix a 3&prime;-endpoint, producing cloned inserts from the cDNA in a vector containing a bacteriophage-specific promoter for subsequent RNA synthesis, generating linearized fragments of the cloned inserts, preparing cRNA, transcribing cDNA from the cRNA using a set of primers, and performing PCR using a 3&prime;-primer whose sequence is derived from the vector and a set of 5&prime;-primers that is derived from the primers used for transcription of cDNA from cRNA. The method can identify changes in expression of mRNA associated with the administration of drugs or with physiological or pathological conditions.

Method for simultaneous sequence-specific identification and display of mRNA's

Cortistatin: neuropeptides

Antibodies or epitope-binding portions thereof raised to a synthetic polypeptide having an amino acid sequence that corresponds substantially to an amino acid residue sequence of at least a portion of a naturally occurring proteinoid and having a molecular weight equal to less than that of the proteinoid are diclosed. That proteinoid contains an amino acid residue sequence translated from a messenger RNA present substantially only in brain cells. Those antibodies or epitope-containing portions bind specifically when admixed with brain cell tissue that includes the naturally occurring proteinoid.

Synthetic polypeptides corresponding to portions of proteinoids

An improved method for the simultaneous sequence-specific identification of mRNAs in a mRNA population allows the visualization of nearly every mRNA expressed by a tissue as a distinct band on a gel whose intensity corresponds roughly to the concentration of the mRNA. In general, the method comprises the formation of cDNA using anchor primers to fix a 3'-endpoint, producing cloned inserts from the cDNA in a vector containing a bacteriophage-specific promoter for subsequent RNA synthesis, generating linearized fragments of the cloned inserts, preparing cRNA, transcribing cDNA from the cRNA using a set of primers, and performing PCR using a 3'-primer whose sequence is derived from the vector and a set of 5'-primers that is derived from the primers used for transcription of cDNA from cRNA. The method can identify changes in expression of mRNA associated with the administration of drugs or with physiological or pathological conditions.

Method for simultaneous identification of differentially expressed mRNAs

An improved method for the simultaneous sequence-specific identification of mRNAs in a mRNA population allows the visualization of nearly every mRNA expressed by a tissue as a distinct band on a gel whose intensity corresponds roughly to the concentration of the mRNA. In general, the method comprises the formation of cDNA using anchor primers to fix a 3'-endpoint, producing cloned inserts from the cDNA in a vector containing a bacteriophage-specific promoter for subsequent RNA synthesis, generating linearized fragments of the cloned inserts, preparing cRNA, transcribing cDNA from the cRNA using a set of 5'-RT primers, and performing PCR using a 3'-PCR primer whose sequence is derived from the vector and a set of 5'-PCR primers that is derived from the 5'-RT primers used for transcription of cDNA from cRNA. The method can identify changes in expression of mRNA associated with the administration of drugs or with physiological or pathological conditions.

Method for simultaneous identification of differentially expresses mRNAs

Cortistatin: nucleic acids that encode these neuropeptides

Method for simultaneous identification of differentially expressed mRNAS

The present invention describes nucleic acid molecules encoding human serotonin receptors, recombinant serotonin receptor proteins, cultured cells expressing recombinant serotonin receptor proteins, antibodies immunoreactive with serotonin receptor proteins, polypeptide serotonin receptor antagonists, oligonucleotide probes used for detecting nucleic acids which encode a human serotonin receptor, and nonhuman transgenic animals which express recombinant human serotonin receptor. Also disclosed are methods for screening for ligand binding to the described serotonin receptors and for serotonin receptor agonists and antagonists, for detection of serotonin receptors in tissues, and for therapeutic treatments involving the described human serotonin receptors.

Growing community of inventors

Cardiff, CA, United States of America

J Gregor Sutcliffe