University of California

Neurofluidics, Inc.

Leland Stanford Junior University

The General Hospital Corporation

Massachusetts General Hospital Corporation

Tanzi, Rudolph E.

William C Mobley

Shivanand Lad

Thomas Saul

Karoly Nikolich

Rudolph Emile Tanzi

Steven L Wagner

Graham Johnson

Soan Cheng

Robert Jason Herr

Nicholas James Mayhew

Ronald Buckle

Ronald J Weigel

Kevin D Rynearson

Har Hiu Dawn Lam

Chengbiao Wu

James C Kauer

Frank M Longo

Mehrdad Shamloo

Ahmad Salehi

Janice Vallette

Mehrdad Faizi

Shivanand P Lad

The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF) by removing target compounds from CSF. The systems provide for a catheter flow path and exchange of a majority volume portion of CSF in the CSF space. The removal and/or delivery of specific compounds can be tailored to the pathology of the specific disease. The removal is targeted and specific, for example, through the use of specific size-exclusion thresholds, antibodies against specific toxins, and other chromatographic techniques, as well as delivery and/or removal of targeted therapeutic agents.

Cerebrospinal fluid purification system

Provided herein are compounds and methods for treating a disorder associated with aberrant A&#x3b2; peptide levels, including Alzheimer's disease.

Potent gamma-secretase modulators

Provided herein are compounds and methods for treating a disorder associated with aberrant A3 peptide levels, including Alzheimer's disease. Provided herein are compositions and methods for treating a disorder associated with aberrant A&#x3b2; peptide levels, including AD. Provided herein are compounds of Formula (A) or a pharmaceutically acceptable salt thereof, wherein, L' is selected from the group consisting of C(O), C(R1)(R2), substituted or unsubstituted &#x2014;C2-6 alkylene-, and substituted or unsubstituted &#x2014;C3-6 cycloalkylene. 

There are provided, inner alia, compounds and methods for lowering total AB peptide production by inhibiting the catalytic activity of gamma-secretase. Since all of the major AB peptide variants, including the pathogenic AB42 as known in the art, are ultimately generated by gamma-secretase-mediated proteolysis of APP-C99 (i.e., the beta-secretase-mediated cleavage product of the amyloid protein precursor IAPPI), one approach to therapeutic intervention (e.g., intervention in Alzheimer's Disease, AD) relates to lowering total AB peptide production by inhibiting the catalytic activity of gamma-secretase.

Gamma-secretase modulators

The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF) by removing target compounds from CSF. The systems provide for a multilumen flow path and exchange of a majority volume portion of CSF in the CSF space. The removal and/or delivery of specific compounds can be tailored to the pathology of the specific disease. The removal is targeted and specific, for example, through the use of specific size-exclusion thresholds, antibodies against specific toxins, and other chromatographic techniques, as well as delivery and/or removal of targeted therapeutic agents.

The invention provides a novel compound having a structure corresponding to Formula (I):(A)-(B)-(C)-(D)&#x2003;&#x2003;(I)or a pharmaceutically acceptable salt or prodrug thereof and methods for using them.

Compounds and uses thereof in modulating levels of various amyloid beta peptide alloforms

A method for enhancing learning or memory of both in a mammal having impaired learning or memory of both from a neuro-degenerative disorder, which entails the step of administering at least one compound or a salt thereof which is a &#x3b2;-adrenergic receptor agonist, partial agonist or receptor ligand in an amount effective to improve the learning or memory or both of said mammal.

Method for enhancing learning and memory impaired by neurodegenerative disorders and compounds and compositions for effecting the same

A method of treating an individual having Down syndrome or Alzheimer's disease, which entails the step of administering an amount of one or more compounds to the individual which improve cognitive functioning in the individual by increasing hippocampal NE levels.

Method of improving cognitive functions in individuals with down syndrome and/or alzheimer's disease

The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF) by removing target compounds from CSF. A multilumen flow path allows exchange of a majority volume portion of CSF in the CSF space. The removal and/or delivery of specific compounds can be tailored to the pathology of the specific disease. The removal is targeted and specific, for example, through the use of specific size-exclusion thresholds, antibodies against specific toxins, and other chromatographic techniques, as well as delivery and/or removal of targeted therapeutic agents.

Neurological dysfunction is prevented or treated by the administration of ligands that activate the GPR30 receptor. Ligands include estrogens and structurally related molecules. Preferably the GPR30 ligand is an orally available drug that can cross into the brain from blood. Screening methods are provided for ligands that do not activate other estrogen receptors, and therefore do not have the classical estrogenic effects attributable to these receptors.

Use of GPR30 receptor ligands to mediate neurotrophic action

Neurological dysfunction is prevented or treated by the administration of ligands that activate the GPR30 receptor. Ligands include, but are not limited to, estrogens and structurally related molecules. In a preferred embodiment, the GPR30 ligand is an orally available drug that can cross into the brain from blood. Of particular interest are ligands that do not activate other estrogen receptors, and therefore do not have the classical estrogenic effects attributable to these receptors.

Method of screening for neuroprotective agents

The present invention provides both agonist and antagonist nerve growth factor peptides. The NGF blocking peptides can be used to inhibit the expression of mRNA and their encoded proteins whose expression is stimulated by NGF, such as .beta.-protein precursor and prion proteins, which proteins or their products are associated with neurodegenerative disorders, whereas the NGF agonist peptides can be used to treat neoplastic disorders such as neuroblastomas.

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La Jolla, CA, United States of America

William C Mobley