Abstract: Provided are methods and compositions from reprogramming human glial cells into human neurons. The reprogramming is achieved using combinations of compounds that can modify signaling via Transforming growth factor beta (TGF-?), Bone morphogenetic protein (BMP), glycogen synthase kinase 3 (GSK-3), and ?-secretase/Notch pathways. The reprogramming is demonstrated using groups of three or four compounds that are chosen from the group thiazovivin, LDN193189, SB431542, TTNPB, CHIR99021, DAPT, VPA, SAG purmorphamine. Reprogramming is demonstrated using the group of LDN193189/CHIR99021/DAPT, the group of B431542/CHIR99021/DAPT, the group of LDN193189/DAPT/SB431542, the group of LDN193189/CHIR99021/SB431542, a three drug combination of SB431542/CHIR99021/DAPT. Reprogramming using functional analogs of the compounds is also provided, as are pharmaceutical formulations that contain the drug combinations.
Type:
Grant
Filed:
September 30, 2019
Date of Patent:
September 14, 2021
Assignee:
The Penn State Research Foundation
Inventors:
Gong Chen, Gang-Yi Wu, Lei Zhang, Jiu-Chao Yin, Hana Yeh, Ning-Xin Ma, Grace Lee
Abstract: The present invention relates to a method for diagnosing a disease, comprising the step detecting in a sample an autoantibody binding to the alpha 3 subunit of the human neuronal Na(+)/K(+) ATPase, an isolated and/or recombinant polypeptide comprising the alpha 3 subunit of the human neuronal Na(+)/K(+) ATPase, a use of a membrane-associated human Na(+)/K(+) ATPase or a variant thereof for the diagnosis of a disease, an isolated and/or recombinant polypeptide comprising the alpha 3 subunit of the human neuronal Na(+)/K(+) ATPase or a variant thereof, for use in the treatment of a disease, an autoantibody binding to said polypeptide and a method for isolating such autoantibody, a pharmaceutical composition, medical or diagnostic device or test kit comprising the polypeptide.
Type:
Grant
Filed:
June 3, 2015
Date of Patent:
September 7, 2021
Assignee:
EUROIMMUN Medizinische Labordiagnostika AG
Inventors:
Lars Komorowski, Madeleine Scharf, Ramona Miske, Yvonne Denno, Inga-Madeleine Dettmann, Christian Probst, Fedor Heidenreich, Ralf Gieß
Abstract: A safe and effective vaccine to prevent, slow, halt or reverse progression of Alzheimer's disease in human patients is disclosed. The vaccine includes A?1-42 or an beta amyloid self epitope (e.g. A?1-15, or other 7-mer or 15-mer peptide epitopes derived from A?1-42) conjugated to an immunogenic carrier (e.g. DT) formulated in a water-in-oil Th2-biased adjuvant/delivery system.
Abstract: Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. Here, novel compositions of tau oligomers and novel mechanisms for tau oligomer nucleation, extension and termination are taught.
Abstract: Recombinant clusterin polypeptides and compositions comprising the same are provided. In some aspects, recombinant clusterin or nucleic acids encoding the same may be used for treating and preventing an abnormality of morphology and function in a mammal with disease (e.g., cardiovascular diseases or alcoholism).
Type:
Grant
Filed:
October 9, 2019
Date of Patent:
August 31, 2021
Assignee:
THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
Abstract: The disclosure relates to a pharmaceutical composition comprising any one or combination of PIF peptides or analogs or pharmaceutically acceptable salts thereof. Methods of treating cellular neurodamage or neurotrauma to the peripheral or central nervous system using the one or a combination of PIF peptide or analogs thereof or pharmaceutically acceptable salts thereof is also disclosed.
Abstract: The invention provides anti-UCH-L1 antibodies and anti-GFAP antibodies and their use in vitro detection of UCH-L1 and GFAP, respectively, in a sample from an individual, such as an individual known or suspected of having a brain injury or damage, for example, neurological damage such as mild traumatic brain injury. Also provided are methods, systems and kits for diagnosing brain injury or damage, such as neurological damage, in an individual with the aforementioned antibodies as well as compositions comprising the anti-UCH-L1 antibodies and anti-GFAP antibodies.
Abstract: The present invention discloses nerve growth factor composition and an injection powder comprising the following components: 10 ?g/mL-100 ?g/mL of a nerve growth factor; 10 mg/mL-80 mg/mL of disaccharide stabilizer; 0 mg/mL-30 mg/mL of an amino acid stabilizer; 0.01 mg/mL-1 mg/mL of surfactant, 10 mg/mL-50 mg/mL of a supporting agent; a pH buffer for maintaining the nerve growth factor composition at 6.0-7.4, and solvent being water. The nerve growth factor composition and the injection powder can avoid the potential risk resulting from the virus of other unknown components carried in albumin by using a disaccharide or a combination of a disaccharide and an amino acid instead of albumin as a stabilizer; not only have protective effect on mNGF, but also can ensure the stability of hNGF and rhNGF in the preparation, transportation and storage processes, and have better medication safety and quality control.
Abstract: Disclosed herein are multifunctional polypeptides comprising a first domain comprising an anti-tau antigen binding domain and a second domain comprising a proteasome-targeting PEST motif, and methods for using these polypeptides in treatment of tauopathies.
Type:
Grant
Filed:
September 8, 2017
Date of Patent:
July 27, 2021
Assignee:
Regenerative Research Foundation
Inventors:
Sally Temple, Anne Messer, David Butler
Abstract: The invention is in the field of methods and preparations for medical treatments, in particular the treatment of idiopathic pulmonary fibrosis (IPF). The invention provides such methods wherein antibodies or fragments thereof that react with selected citrullinated epitopes are used in the treatment of IPF. Antibodies against citrullinated epitopes situated at the amino terminus of histone polypeptides H2A and H4 were found to be particularly useful. The invention therefore relates to an antibody specifically reactive with a citrullinated epitope on the N-terminus of deiminated histone H2A or H4 for use in the prevention or treatment of idiopathic pulmonary fibrosis.
Type:
Grant
Filed:
December 11, 2015
Date of Patent:
July 20, 2021
Assignee:
Citryll B.V.
Inventors:
Renato Gerardus Silvano Chirivi, Jozef Maria Hendrik Raats
Abstract: The present invention describes a method of treating, preventing, reducing the likelihood of or alleviating a symptom of Alzheimer's disease and associated conditions by increasing OPN expression. The invention further provides for a method of improving cognitive function in a subject in need thereof.
Type:
Grant
Filed:
May 22, 2017
Date of Patent:
July 13, 2021
Assignee:
CEDARS-SINAI MEDICAL CENTER
Inventors:
Maya Koronyo, Altanchimeg Rentsendorj, Yosef Koronyo, Keith Black
Abstract: The invention relates to humanized antibodies that bind to an epitope at the N-terminus of pyroglutamated amyloid beta (A? N3pE) peptide and to preventive and therapeutic treatment of diseases and conditions that are related to accumulation and deposition of amyloid peptides, such as amyloidosis, a group of disorders and abnormalities associated with pyroglutamated amyloid peptide, like Alzheimer's disease, Down's syndrome, cerebral amyloid angiopathy and other related aspects. More specifically, it pertains to the use of humanized monoclonal antibodies to bind pyroglutamated amyloid beta peptide in plasma, brain, and cerebrospinal fluid to prevent accumulation or to reverse deposition of A? N3pE within the brain and in various tissues in the periphery, and to alleviate amyloidosis. The present invention further pertains to diagnostic assays for the diagnosis of amyloidosis using the humanized antibodies of the invention.
Type:
Grant
Filed:
January 16, 2020
Date of Patent:
June 29, 2021
Inventors:
Martin Kleinschmidt, Jens-Ulrich Rahfeld, Anke Piechotta, Stephan Schilling, Stephen Gillies
Abstract: A method of treating and/or preventing neurological conditions, comprising administering to a subject in need thereof a therapeutically effective amount of a p75 extracellular domain (p75ECD) or a functional fragment, variant, analogue or derivative thereof. Also provided is a method of diagnosing and/or prognosing Alzheimer's disease (AD) in a test subject comprising comparing the concentration of p75ECD and/or p75FL and/or the ratio of p75ECD:p75FL in a biological sample of the test subject to non-demented control subject(s).
Abstract: The present invention relates to the intrathecal (IT) administration of recombinant enzyme to treat lysosomal storage disorders. In an exemplary embodiment, intrathecal administration of human ?-L-iduronidase (rhIDU) injections in MPS I affected animals resulted in significant enzyme uptake, significant rh-iduronidase activity in brain and meninges and a decrease of glycosaminoglycan (GAG) storage in cells of MPS I subjects to that of normal subjects. Intrathecal administration proved more effective than intravenous treatment at alleviating MPS I symptoms, indicating it is a useful method of treating lysosomal storage disorders.
Abstract: Disclosed are conjugates and compositions comprising an amyloid beta binding protein conjugated to a MerTK ligand. Disclosed are methods of clearing amyloid beta aggregates from a subject comprising administering a therapeutically effective amount of the conjugates and compositions comprising an amyloid beta binding protein conjugated to a MerTK ligand. Disclosed are methods of treating Alzheimer's Disease comprising administering to a subject in need thereof a therapeutically effective amount of conjugates and compositions comprising an amyloid beta binding protein conjugated to a MerTK ligand.
Type:
Grant
Filed:
November 11, 2016
Date of Patent:
June 15, 2021
Assignee:
The Board Of Regents Of The Nevada System Of Higher Education On Behalf Of The University of Nevada
Abstract: The application relates to markers for seizures and epilepsy. Polypeptide expression panels or arrays are provided, comprising one or more probes capable of binding specific polypeptides in blood plasma or blood serum of a mammalian subject. Also provided are methods for detecting seizure, methods for predicting seizure, use of sICAM-5 in the treatment of seizure, methods for assessing the effectiveness of a treatment of seizure, and diagnostic kits.
Type:
Grant
Filed:
May 11, 2018
Date of Patent:
June 15, 2021
Assignee:
The Trustees of the University of Pennsylvania
Abstract: A composition and a method for the treatment of a neurodegenerative disorder is provided. The composition includes an inhibitor of RANTES and/or an inhibitor of eotaxin. The method includes administering a composition comprising an inhibitor of RANTES and/or an inhibitor of eotaxin to the subject in need thereof to treat the neurodegenerative disorder.
Abstract: The present invention relates to bispecific antibodies that bind to transferrin receptor and BACE1 and methods of using the same.
Type:
Grant
Filed:
November 18, 2015
Date of Patent:
May 18, 2021
Assignees:
Genentech, Inc., Adimab LLC
Inventors:
Yichin Liu, Jasvinder Atwal, Cecilia Pui Chi Chiu, Ryan J. Watts, Yan Wu, Eric Krauland, Michael Feldhaus, Yin Zhang, Joy Yu Zuchero, Jessica Couch, Mark S Dennis, James A Ernst, Gregory A Lazar
Abstract: The present invention aims to obtain an anti-repulsive guidance molecule a (RGMa) antibody having a high binding activity and few side effects which can be used as a medicine for preventing, treating, or preventing the relapse of neurological or immunological diseases. The problem is solved by providing an isolated RGMa binding protein which does not inhibit binding between RGMa and neogenin but neutralizes the neurite outgrowth inhibiting activity of RGMa, preferably by providing an anti-RGMa antibody which has complementarity determining regions having amino acid sequences of SEQ ID NOS: 30-35 or SEQ ID NOS: 36-40 in Sequence Listing, and SFG.
Type:
Grant
Filed:
March 19, 2019
Date of Patent:
May 18, 2021
Assignees:
MITSUBISHI TANABE PHARMA CORPORATION, OSAKA UNIVERSITY, NATIONAL UNIVERSITY CORPORATION CHIBA UNIVERSITY