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1. (WO2019067844) ENDOTHELIAL FACILITATION IN NEURODEGENERATIVE DISEASES BY CEREBRAL BLOOD FLOW ENHANCEMENT
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Pub. No.: WO/2019/067844 International Application No.: PCT/US2018/053324
Publication Date: 04.04.2019 International Filing Date: 28.09.2018
IPC:
A61K 31/198 (2006.01) ,A61K 31/366 (2006.01) ,A61K 31/48 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
185
Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
19
Carboxylic acids, e.g. valproic acid
195
having an amino group
197
the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid (GABA), beta-alanine, epsilon-aminocaproic acid, pantothenic acid
198
Alpha-amino acids, e.g. alanine, edetic acid (EDTA)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
33
Heterocyclic compounds
335
having oxygen as the only ring hetero atom, e.g. fungichromin
365
Lactones
366
having six-membered rings, e.g. delta-lactones
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
33
Heterocyclic compounds
395
having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
435
having six-membered rings with one nitrogen as the only ring hetero atom
47
Quinolines; Isoquinolines
48
Ergoline derivatives, e.g. lysergic acid, ergotamine
Applicants:
UNIVERSITY OF MASSACHUSETTS [US/US]; One Beacon Street, 31st Floor Boston, MA 02108, US
Inventors:
DRACHMAN, David; US
Agent:
HOWERTON, Thomas C.; US
HOWERTON, Thomas, C.; US
HAMDAN, Maha, A.; US
KELLY, Gilbert, Thomson; US
Priority Data:
62/564,61528.09.2017US
Title (EN) ENDOTHELIAL FACILITATION IN NEURODEGENERATIVE DISEASES BY CEREBRAL BLOOD FLOW ENHANCEMENT
(FR) FACILITATION ENDOTHÉLIALE DANS DES MALADIES NEURODÉGÉNÉRATIVES PAR AMÉLIORATION DU FLUX SANGUIN CÉRÉBRAL
Abstract:
(EN) The "amyloid hypothesis" has dominated Alzheimer research for more than 20 years, and proposes that amyloid is the toxic cause of neural/synaptic damage and dementia. Despite discrepancies in the proposed mechanism, and failed clinical trials, amyloid continues to be considered the cause of a degenerative cascade. The present invention proposes that AD is precipitated by impaired microvascular function, resulting primarily from decreased Notch-related angiogenesis. With impaired microvasculature, a lack of vascular endothelial-derived trophic factors and decreased cerebral blood flow cause the atrophy of neural structures. Therapeutic strategies are proposed that focus on supporting normal angiogenesis.
(FR) L'"hypothèse amyloïde" a dominé la recherche d'Alzheimer pendant plus de 20 ans, et propose que l'amyloïde est la cause toxique de lésions neuronales/synaptiques et de démence. Malgré des divergences dans le mécanisme proposé, et des essais cliniques défaillants, l'amyloïde continue à être considérée comme la cause d'une cascade dégénérative. La présente invention propose que la maladie d'alzheimer soit provoquée par une fonction microvasculaire altérée, ce qui résulte principalement d'une diminution de l'angiogenèse liée à Notch. Avec une microvascularisation altérée, un manque de facteurs trophiques dérivés de l'endothélium vasculaire et un flux sanguin cérébral diminué provoquent l'atrophie de structures neurales. L'invention concerne des stratégies thérapeutiques qui se concentrent sur le support de l'angiogenèse normale.
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)