公开(公告)号：US20220025379A1

公开(公告)日：2022-01-27

申请号：US17413384

申请日：2019-12-11

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  Zhengshan LIU

IPC: C12N15/113 ,  A61P25/18 ,  A61K31/713

Abstract: The present disclosure relates to methods of restoring K+ uptake by glial cells in a subject. These methods involve administering, to the subject, a SMAD4 inhibitor under conditions effective to restore K+ uptake by said glial cells. The present disclosure is also directed to methods of treating or inhibiting the onset of a neuropsychiatric disorder in a subject. These methods involve administering, to a subject in need thereof, a SMAD4 inhibitor under conditions effective to treat or inhibit the onset of the neuropsychiatric disorder in the subject.

公开(公告)号：US20230226116A1

公开(公告)日：2023-07-20

申请号：US18046930

申请日：2022-10-16

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  John MARIANI ,  Nguyen P.T. HUYNH

IPC: A61K35/30 ,  C12N5/079 ,  C12N15/90 ,  C12N15/11 ,  C12N9/22 ,  A61P25/28

CPC classification number: A61K35/30 ,  C12N5/0622 ,  C12N15/907 ,  C12N15/11 ,  C12N9/22 ,  A61P25/28 ,  C12N2506/02 ,  C12N2310/20 ,  C12N2800/80

Abstract: A method for rejuvenating glial progenitor cells and rejuvenated glial progenitor cells rejuvenated by such method are disclosed. The method comprises introducing a population of genetically modified glial progenitor cells into the brain and/or brain stem of a subject, wherein the genetically modified glial progenitor cells have increased expression of one or more genes compared to the same type of glial progenitor cells that have not been genetically modified, and wherein the one or more genes are selected from the group consisting of ARX, CEBPZ, DLX1, DLX2, ELK1, ETS1, ETV4, KLF16, MYBL2, MYC, NFYB, POU3F1, SMAD1, SOX3, SP5, TCF12, TFDP1, TP53, ZIC3 and ZNF195.

公开(公告)号：US20230212568A1

公开(公告)日：2023-07-06

申请号：US17968984

申请日：2022-10-19

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  John N. MARIANI

IPC: C12N15/113 ,  C12N15/86 ,  A61P25/28

CPC classification number: C12N15/113 ,  A61P25/28 ,  C12N15/86 ,  C12N2310/141 ,  C12N2320/35 ,  C12N2740/15043

Abstract: The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of inducing rejuvenation in a population of adult glial progenitor cells, may comprise: administering, to the population of adult glial progenitor cells, one or more nucleic acid molecules encoding microRNAs, wherein administering suppresses the signal transducer and activator of transcription 3 (STAT3) signaling pathway; and/or administering microRNAs, wherein administering suppresses the E2F transcription factor 6 (E2F6) signaling pathway; and/or administering microRNAs, wherein administering suppresses the Myc-associated factor X (MAX) signaling pathway, wherein said one or more nucleic acid molecules are administered in an amount sufficient to induce rejuvenation in the population of adult glial progenitor cells.

公开(公告)号：US20230190961A1

公开(公告)日：2023-06-22

申请号：US18047744

申请日：2022-10-19

Applicant: University of Rochester

Inventor： Steven A. GOLDMAN ,  John N. Mariani

IPC: A61K48/00 ,  C12N15/86 ,  C12N9/10 ,  C12N9/80 ,  A61K38/17 ,  A61K38/50 ,  A61K38/45 ,  A61P25/28

CPC classification number: A61K48/0058 ,  C12N15/86 ,  C12N9/1007 ,  C12N9/80 ,  C12Y305/01098 ,  A61K38/1709 ,  A61K38/50 ,  A61K38/45 ,  A61K48/0066 ,  A61P25/28 ,  C12N2740/15043 ,  C12N2740/15032

Abstract: The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of treating a subject having a myelin deficiency, may comprise expressing, in glial progenitor cells of the subject, one or more transcription factors selected from the group consisting of B-cell lymphoma/leukemia 11A (BCL11A), histone deacetylase 2 (HDAC2), histone-lysine N-methyltransferase EZH2 (EZH2), myc proto-oncogene protein (MYC), high mobility group protein HMGI-C (HMGA2), nuclear factor 1 B-type (NFIB), and transcriptional enhancer factor TEF-4 10 (TEAD2), wherein said expressing is effective to induce myelination in the subject, thereby treating the myelin deficiency.

公开(公告)号：US20200048605A1

公开(公告)日：2020-02-13

申请号：US16659110

申请日：2019-10-21

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  Su WANG

IPC: C12N5/079 ,  A61K9/00 ,  A61K35/30

Abstract: The present disclosure relates to a preparation of CD140a/PDGFRα positive cells that comprises oligodendrocyte progenitor cells co-expressing OLIG2 and CD140a/PDGFRα. The preparation of cells is derived from pluripotent cells that were derived from skin cells, fibroblasts, umbilical cord blood, peripheral blood, bone marrow, or other somatic cells. The cell preparation has an in vivo myelination efficiency that is equal to or greater than the in vivo myelination efficiency of a preparation of A2B5+/PSA-NCAM− sorted fetal human tissue derived oligodendrocyte progenitor cells. Methods of making, isolating and using the disclosed cell preparation are also described.

公开(公告)号：US20230173110A1

公开(公告)日：2023-06-08

申请号：US18096718

申请日：2023-01-13

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN

IPC: A61K49/00 ,  A61K35/30 ,  A61K35/545 ,  A01K67/027 ,  C12N5/079 ,  G01N33/50 ,  C12N5/07 ,  A61K45/06

CPC classification number: A61K49/0008 ,  A61K35/30 ,  A61K35/545 ,  A01K67/0271 ,  C12N5/0622 ,  G01N33/50 ,  G01N33/5085 ,  C12N5/06 ,  A61K45/06 ,  A01K2207/12 ,  A01K2267/0318 ,  G01N2800/28 ,  G01N2800/2814 ,  G01N2800/2821 ,  G01N2800/2835 ,  A01K2207/15 ,  A01K2227/105

Abstract: The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

公开(公告)号：US20230159890A1

公开(公告)日：2023-05-25

申请号：US18046928

申请日：2022-10-16

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  John Mariani

IPC: C12N5/079 ,  A61P25/28 ,  C12N5/0797

CPC classification number: C12N5/0622 ,  A61P25/28 ,  C12N5/0623 ,  C12N2510/00

Abstract: A genetically modified glial cells, and use of such cells for rejuvenating glial cell population or treating glial cell-related disorders are disclosed. A method of treating a disorder of the brain and/or brain stem in a subject by introducing a population of genetically modified glial progenitor cells into the brain and/or brain stem of the subject, wherein the genetically modified glial progenitor cells have increased expression of one or more genes compared to the same type of glial progenitor cells that have not been genetically modified, wherein said increased expression of the one or more genes in the genetically modified glial progenitor cells confer competitive advantage over native or already resident glial progenitor cells in the subject.

公开(公告)号：US20230133695A1

公开(公告)日：2023-05-04

申请号：US18047749

申请日：2022-10-19

Applicant: University of Rochester

Inventor： Steven A. GOLDMAN ,  John N. Mariani ,  Abdellatif Benraiss

IPC: C12N15/113 ,  C12N15/86 ,  A61P25/00

Abstract: The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of inducing rejuvenation in a population of adult glial progenitor cells may comprise administering, to the population of adult glial progenitor cells, an effective amount of an agent that suppresses one or more transcription factors selected from the group consisting of (i) zinc finger protein 274 (ZNF274), (ii) Myc-associated factor X (MAX), (iii) E2F transcription factor 6 (E2F6), (iv) zinc finger protein Aiolos (IKZF3), and (v) signal transducer and activator of transcription 3 (STAT3).

公开(公告)号：US20200048604A1

公开(公告)日：2020-02-13

申请号：US16659062

申请日：2019-10-21

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  Su WANG

IPC: C12N5/079 ,  A61K9/00 ,  A61K35/30

Abstract: The present disclosure relates to a preparation of CD140a/PDGFRα positive cells that comprises oligodendrocyte progenitor cells co-expressing OLIG2 and CD140a/PDGFRα. The preparation of cells is derived from pluripotent cells that were derived from skin cells, fibroblasts, umbilical cord blood, peripheral blood, bone marrow, or other somatic cells. The cell preparation has an in vivo myelination efficiency that is equal to or greater than the in vivo myelination efficiency of a preparation of A2B5+/PSA-NCAM− sorted fetal human tissue derived oligodendrocyte progenitor cells. Methods of making, isolating and using the disclosed cell preparation are also described.

公开(公告)号：US20160045506A1

公开(公告)日：2016-02-18

申请号：US14776961

申请日：2014-03-14

Applicant: UNIVERSITY OF ROCHESTER

Inventor： Steven A. GOLDMAN ,  Romane AUVERGNE

IPC: A61K31/519 ,  A61K31/4439 ,  A61K31/443

CPC classification number: A61K31/519 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4439 ,  A61K38/00 ,  C07K14/705 ,  G01N2333/726 ,  G01N2500/02 ,  G01N2800/7028

Abstract: The present invention relates to a method of treating glioma in a subject. The method comprises selecting a subject having a glioma, providing an inhibitor of binding between a PAR-1 receptor and a ligand of the PAR-1 receptor, and administering the inhibitor to the selected subject under conditions effective to treat the glioma and/or prevent spread of tumor cells. Methods for inhibiting proliferation of glioma cells and/or precursors thereof and a method of screening for compounds suitable for treating glioma in subjects are also disclosed.

Abstract translation: 本发明涉及治疗受试者中胶质瘤的方法。 该方法包括选择具有神经胶质瘤的受试者，提供PAR-1受体和PAR-1受体的配体之间的结合抑制剂，以及在有效治疗胶质瘤和/或预防的条件下将抑制剂施用于所选择的受试者 肿瘤细胞扩散。 还公开了抑制神经胶质瘤细胞和/或其前体的增殖的方法和筛选适合于治疗受试者中胶质瘤的化合物的方法。