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1. (WO2019023793) GENERATION OF OLIGODENDROGENIC NEURAL PROGENITOR CELLS
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Pub. No.: WO/2019/023793 International Application No.: PCT/CA2018/050926
Publication Date: 07.02.2019 International Filing Date: 30.07.2018
IPC:
C12N 5/0797 (2010.01) ,A61K 35/30 (2015.01) ,A61P 35/00 (2006.01) ,A61P 25/28 (2006.01)
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5
Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07
Animal cells or tissues
071
Vertebrate cells or tissues, e.g. human cells or tissues
079
Neural cells
0797
Stem cells; Progenitor cells
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
35
Medicinal preparations containing material or reaction products thereof with undetermined constitution
12
Materials from mammals or birds
30
Nerves; Brain
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25
Drugs for disorders of the nervous system
28
for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Applicants:
UNIVERSITY HEALTH NETWORK [CA/CA]; 190 Elizabeth Street R. Fraser Elliott Building - Room 1S-417 Toronto, Ontario M5G 2C4, CA
Inventors:
FEHLINGS, Michael G.; CA
KHAZAEI, Mohamad; CA
Agent:
BERESKIN & PARR LLP/S.E.N.C.R.L., S.R.L.; 40th Floor 40 King Street West Toronto, Ontario M5H 3Y2, CA
Priority Data:
3,006,89701.06.2018CA
62/541,47704.08.2017US
Title (EN) GENERATION OF OLIGODENDROGENIC NEURAL PROGENITOR CELLS
(FR) GÉNÉRATION DE CELLULES PROGÉNITRICES DE NEURONES OLIGODENDROGÉNIQUES
Abstract:
(EN) Provided herein are methods of producing, compositions comprising and uses of oligodendrogenic neural progenitor cells (o-NPCs), made using a combination of PDGFR agonist and thyroxin or a thyroxin analogue. The method includes; obtaining ventralized neural progenitor cells (NPCs), the ventralized NPCs expressing Sox2, Nkx6-1, decreased level of Pax6 compared to unpatterned NPCs, and elevated expression of HoxA4 compared to unpatterned NPCs; culturing the ventralized NPCs for about 12 to about 16 days (days 26-40 of Fig. 7; days 12 to 27 of Fig. 10) in neural expansion media (NEM) supplemented with i) PDGFR agonist for the about 12 to about 16 days and ii) thyroxine or a thyroxine analogue for the latter about 7 to about 9 days, to produce o-NPC expressing Sox2 and Nkx2.2, decresed level of Pax6 and Nkx6.1 compared to ventralized NPCs and elevated level of HoxA4 and Olig2 compared to ventralized NPCs.
(FR) La présente invention concerne des procédés de production, des compositions comprenant et des utilisations de cellules progénitrices de neurones oligodendrogéniques (o-NPC), fabriquées en utilisant une combinaison d’agoniste PDGFR et de thyroxine ou un analogue de thyroxine. Le procédé comprend : l’obtention de cellules progénitrices de neurones ventralisées (NPC), les NPC ventralisées exprimant Sox2, Nkx6-1, un niveau réduit de Pax6 comparées aux NPC non modelées, et une expression élevée de HoxA4 comparées aux NPC non modelées ; la culture des NPC ventralisées durant environ 12 à environ 16 jours (jours 26 à 40 de la FIG. 7 ; jours 12 à 27 de la FIG. 10) dans un milieu d’expansion neural (NEM) enrichi de i) l'agoniste PDGFR durant les environ 12 à environ 16 jours et ii) de la thyroxine ou un analogue de thyroxine pour ce dernier environ 7 à environ 9 jours, pour produire des o-NPC exprimant Sox2 et Nkx2.2, un niveau réduit de Pax6 et Nkx6.1 comparées aux NPC ventralisées et un niveau élevé de HoxA4 et Olig2 comparées aux NPC ventralisées.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)