WIPO logo
Mobile | Deutsch | Español | Français | 日本語 | 한국어 | Português | Русский | 中文 | العربية |
PATENTSCOPE

Search International and National Patent Collections
World Intellectual Property Organization
Search
 
Browse
 
Translate
 
Options
 
News
 
Login
 
Help
 
Machine translation
1. (WO2006081444) FARNESYLTRANSFERASE INHIBITORS FOR TREATMENT OF LAMINOPATHIES, CELLULAR AGING AND ATHEROSCLEROSIS
Latest bibliographic data on file with the International Bureau   

Pub. No.:    WO/2006/081444    International Application No.:    PCT/US2006/002977
Publication Date: 03.08.2006 International Filing Date: 27.01.2006
IPC:
A61K 31/4704 (2006.01), A61K 31/473 (2006.01), A61K 31/445 (2006.01), A61K 31/255 (2006.01), A61K 31/221 (2006.01), A61P 43/00 (2006.01), A61P 9/10 (2006.01), A61P 21/00 (2006.01), A61P 25/00 (2006.01)
Applicants: THE GOVERNMENT OF THE USA AS REPRESENTED BY THE SECRETARY OF THE DEPT. OF HEALTH AND HUMAN SERVICES [US/US]; NATIONAL INSTITUTES OF HEALTH, OFFICE OF TECHNOLOGY TRANSFER, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804 (US) (For All Designated States Except US).
PROGERIA RESEARCH FOUNDATION [US/US]; Po Box 3453, Prabody, MA 01961-3453 (US) (For All Designated States Except US).
THE REGENTS OF THE UNIVERSITY OF MICHIGAN [US/US]; WOLVERINE TOWER, ROOM 2071, 3003 S. State Street, Ann Arbor, MI 48109-1290 (US) (For All Designated States Except US).
THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL [US/US]; OFFICE OF TECHNOLOGY DEVELOPMENT, 308 BYNUM HALL, Cb 4105, Chapel Hill, North Carolina 27599-4105 (US) (For All Designated States Except US).
GORDON, Leslie, B. [US/US]; (US) (For US Only).
COLLINS, Francis, S. [US/US]; (US) (For US Only).
GLOVER, Thomas [US/US]; (US) (For US Only).
GLYNN, Michael, W. [US/US]; (US) (For US Only).
CAPELL, Brian, C. [US/US]; (US) (For US Only).
COX, Adrienne, D. [US/US]; (US) (For US Only).
DER, Channing, J. [US/US]; (US) (For US Only)
Inventors: GORDON, Leslie, B.; (US).
COLLINS, Francis, S.; (US).
GLOVER, Thomas; (US).
GLYNN, Michael, W.; (US).
CAPELL, Brian, C.; (US).
COX, Adrienne, D.; (US).
DER, Channing, J.; (US)
Agent: HARDING, Tanya, M; KLARQUIST SPARKMAN, LLP, ONE WORLD TRADE CENTER, SUITE 1600, 121 SW Salmon Street, Portland, OR 97204 (US)
Priority Data:
60/648,307 28.01.2005 US
60/707,192 09.08.2005 US
Title (EN) FARNESYLTRANSFERASE INHIBITORS FOR TREATMENT OF LAMINOPATHIES, CELLULAR AGING AND ATHEROSCLEROSIS
(FR) INHIBITEURS DE FARNESYL TRANSFERASE DESTINE A TRAITER LES LAMINOPATHIES, LE VIEILLISSEMENT CELLULAIRE ET L'ATHEROSCLEROSE
Abstract: front page image
(EN)Although it can he farnesylated, the mutant lamin A protein expressed in Hutchison Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called 'progerin') that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non- laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.
(FR)Bien qu'elle puisse être farnésylée, la protéine A de lamine mutante exprimée dans le syndrome d'Hutchinson-Gilford (HGPS) ne peut pas être défarnésylé parque la mutation caractéristique entraîne la suppression d'un site de clivage nécessaire à la liaison de la protéase ZMPSTE24 et à mettre en oeuvre la défarnésylation. On obtient une protéine farnésylée aberrante (appelée 'progérine') qui modifie la fonction A de lamine normale en tant que dominant négatif, et qui prend en charge sa propre fonction aberrante par son association avec la membrane nucléaire. La rétention de farnésylation, et d'autres propriétés anormales potentielles de la progérine et d'autres produits de protéine génique de lamine anormale, produit des maladies. Des inhibiteurs de farnésyl transférase (FTI) (à la fois des effecteurs directs et des inhibiteurs indirects) vont inhiber la formation de progérine, entraîner une réduction de protéine A lamine, et/ou une augmentation de protéine A prélamine. La réduction de la quantité de protéine aberrante améliore les effets cellulaires entraînés par l'expression de la progérine de façon similaire le traitement avec des FTI devrait améliorer l'état pathologique de la progéria et d'autres laminopathies. En outre, des éléments d'athérosclérose et de vieillissement chez des individus non laminopathiques vont être améliorés après traitement au moyen de inhibiteurs de farnésyl transférase.
Designated States: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, LV, MC, NL, PL, PT, RO, SE, SI, SK, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Publication Language: English (EN)
Filing Language: English (EN)