Abstract: Treatment of subjects experiencing cerebral ischemia is improved when the treatment employs a thrombolytic and an inhibitor against vascular endothelial growth factor receptor signal transduction (VEGF-RST) at a reduced, low dosage compared to that used to treat cancer patients. The treatment is also improved to permit point-of-care use by formulating protein drugs for long term stability at room temperature, providing doses appropriate for the method, and by combining the therapeutic agents with a point-of-care diagnostic for blood brain barrier integrity.

Abstract: This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNF? antagonist. The NGF antagonist and the TNF? antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNF? antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNF? antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNF? antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNF? antagonist administered alone.

Abstract: The present invention relates to a recombinant fusion protein comprising a fragment of the cardioprotective protein neuregulin-1 (NRG-1) fused to a monoclonal antibody (mAb) backbone and to a method of treating a disease or condition in a subject in need thereof comprising administering a therapeutically effective amount of the recombinant fusion protein or the pharmaceutical composition comprising the recombinant fusion protein disclosed herein.

Abstract: A method for treating Alzheimer's disease (AD) by administering to an AD patient a PKC activator, such as a bryostatin-1, without administering a NMDA receptor antagonist, such as memantine.

Abstract: In some aspects, a cross-species platform useful for drug discovery in neurodegenerative diseases is described.

Abstract: The invention relates to antibodies, antibody fragments and binding agents that specifically recognize TDP-43 associated with frontotemporal dementia (FTD), but not TDP-43 associated with amyotrophic lateral sclerosis (ALS) or TDP-43 associated with healthy human brain tissue, and antibodies, antibody fragments and binding agents that specifically recognize TDP-43 associated with ALS, but not TDP-43 associated FTD or TDP-43 associated with healthy human brain tissue.

Abstract: Disclosed are reactive miniproteins, and peptides comprising them. The miniproteins and peptides are amino acid sequences not found in nature that are able to undergo SNAr chemistry and other nucleophilic based reactions. Also disclosed are conjugates comprising at least one of the reactive miniproteins or peptides, and methods of forming these conjugates.

Abstract: Compositions and methods effective to provide therapeutic benefit for disorders of the central nervous system via oral or systemic delivery of therapeutic proteins produced in plastids are disclosed.

Abstract: The present invention relates to antibody-based molecules (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to the truncated Asp421 epitope of Tau. Such antibody-based molecules are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis and/or treatment of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The antibody-based molecules of the present invention have particular utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

Abstract: A fusion protein used for preventing and treating Alzheimer's disease, a preparation method therefor, and an application thereof. The fusion protein comprises the extracellular domain of human p75NTR human IL-33 and a linker peptide respectively connected to the carboxyl terminus of the p75NTR-ECD and the amino terminus of the human IL-33. The amino acid sequence of the p75NTR-ECD is as shown in SEQ ID NO: 1, and the nucleotide sequence is as shown in SEQ ID NO: 2. The amino acid sequence of the human IL-33 is as shown in SEQ ID NO: 3, and the nucleotide sequence is as shown in SEQ ID NO. 4. The invention overcomes the defects of the p75NTR-ECD or a fusion protein p75NTR-ECD-FC), for preventing and treating Alzheimer's disease. In addition, the functions of the IL-33 and the p75NTR-ECD are combined together, and the biological activity for preventing and treating Alzheimer's disease is significantly increased.

Abstract: In some embodiments, methods of stimulating fluid intake in a subject in need thereof are described. The methods can comprise stimulating a nitric oxide synthase (nNOS)-positive neuron of the median preoptic nucleus (MnPO). In some embodiments, methods of inhibiting fluid intake in a subject in need thereof are described. The methods can comprise inhibiting stimulation of an nNOS-positive neuron of the MnPO.

Abstract: The present invention pertains to a method for standardizing the sensitivity of induced pluripotent stem cell (iPS)-derived neurons to a neurotoxin polypeptide, comprising the steps of: a) cultivating different batches of induced pluripotent stem cell-derived neurons in a cell culture medium comprising GT1b for at least 3 hours; b) contacting the different batches of induced pluripotent stem cell-derived neurons of step a) with a neurotoxin polypeptide; c) cultivating the different batches of induced pluripotent stem cell-derived neurons of step b) for at least 24 hours in the presence of GT1b under conditions which allow for the neurotoxin polypeptide to exert its biological activity, thereby standardizing the sensitivity of the induced pluripotent stem cell-derived neurons to a neurotoxin polypeptide.

Abstract: The present invention provides soluble RAGE-Fc fusion proteins with increased stability and extended half-life capable of binding endogenous RAGE ligands with high apparent affinity. The present invention also provides methods of making and using stable, soluble RAGE-Fc fusion proteins. These soluble RAGE-Fc fusion proteins are useful as therapeutics based on their ability to bind endogenous RAGE ligands.

Abstract: The present invention relates to novel D-enantiomeric A-beta-oligomer-binding peptides, homologs, fragments, parts and polymers thereof and use thereof.

Abstract: Provided herein are compositions and methods related to treating repeat expansion diseases that feature the sequestration of Muscleblind-like (MBNL) proteins by the toxic repeat RNA transcripts within distinct nuclear foci that are expressed from the expanded repeat tracts. Certain compositions of synthetic MBLN proteins can be used to displace endogenous MBNL from the toxic RNAs or replace endogenous MBNL within the cell for normal function.

Abstract: The present invention relates to antibody-based probes (including single domain antibody fragment, scFv molecules, antibodies, antibody fragments, diabodies, and the epitope-binding domains thereof) that are capable of immunospecifically and selectively binding to a phosphoserine-containing epitope of Tau, such as, for example, Tau-phospho-serine 396/404 peptide. Such imaging ligands are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis of Alzheimer's disease or other tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The scFv molecules of the present invention have utility as diagnostic markers for, Alzheimer's disease and related tauopathies and as pharmaceutical compositions for the treatment of such conditions.

Abstract: The invention provides methods of detecting alpha-synuclein using a capture antibody and a reporter antibody. The capture antibody binds preferentially to full-length alpha-synuclein phosphorylated at residue 129 (PS129 alpha-synuclein) over unphosphorylated full-length alpha-synuclein. The 11A5 antibody is an example of a suitable capture antibody. The reporter antibody binds to an epitope within residues 40-55 of alpha-synuclein. The 23E8 antibody is an example of such an antibody. Because only a small proportion of alpha-synuclein is phosphorylated high sensitivity of detection below picomolar is advantageous.

Abstract: The invention relates to in vitro methods for measuring the in vivo metabolism of tau in a subject.

Abstract: Herein is reported a bispecific antibody comprising a first binding specificity that specifically binds to a haptenylated payload and a second binding specificity that specifically binds to a blood brain barrier receptor.

Abstract: The present invention is directed to a biomarker and kit for diagnosing, monitoring and/or staging Alzheimer's disease comprising redox-reactive autoantibodies. The present invention is also directed to a method for diagnosing, monitoring and/or staging Alzheimer's disease which comprises conducting a blood test using the same.