Gene therapy research for Duchenne and Becker muscular dystrophies

被引:20
作者
Karpati, G
Gilbert, R
Petrof, BJ
Nalbantoglu, J
机构
[1] ROYAL VICTORIA HOSP,DEPT MED,DIV RESP,MONTREAL,PQ H3A 1A1,CANADA
[2] MCGILL UNIV,MEAKINS CHRISTIE LABS,MONTREAL,PQ,CANADA
关键词
D O I
10.1097/00019052-199710000-00013
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Gene therapy is a promising option for the definitive treatment of Duchenne and Becker muscular dystrophies. Presently, gene therapy for Duchenne and Becker muscular dystrophies is still in the preclinical stage with dystrophin-deficient animals (the mdx mouse and a golden retriever dog strain) serving as convenient models. The thrust of research during the past 18 months has focused on two approaches: adenovirus-mediated dystrophin gene transfer and upregulation of a natural dystrophin analogue, utrophin. In the area of adenovirus-mediated gene transfer, substantial progress has been made in characterizing and mitigating the deleterious immune responses to the vector and transgene proteins. Furthermore, new adenovirus vectors have been created with reduced immunogenicity and increased insert gene capacity, which enhance the longevity of the transgene expression. Additional efforts are underway to develop safe and efficient routes of administration of the adenovirus vector carrying the dystrophin expression cassette. The prospects of utrophin upregulation as an attractive strategy for treatment of Duchenne and Becker muscular dystrophies was greatly enhanced by the demonstration of a substantial mitigation of the dystrophic phenotype of the transgenic mdx mouse overexpressing utrophin.
引用
收藏
页码:430 / 435
页数:6
相关论文
共 64 条
[21]   Human gene therapy - An immature genie, but certainly out of the bottle [J].
Friedmann, T .
NATURE MEDICINE, 1996, 2 (02) :144-147
[22]   Biology of adenovirus vectors with E1 and E4 deletions for liver-directed gene therapy [J].
Gao, GP ;
Yang, YP ;
Wilson, JM .
JOURNAL OF VIROLOGY, 1996, 70 (12) :8934-8943
[23]   TRANSIENT EXPRESSION OF GENES TRANSFERRED IN-VIVO INTO HEART USING FIRST-GENERATION ADENOVIRAL VECTORS - ROLE OF THE IMMUNE-RESPONSE [J].
GILGENKRANTZ, H ;
DUBOC, D ;
JUILLARD, V ;
COUTON, D ;
PAVIRANI, A ;
GUILLET, JG ;
BRIAND, P ;
KAHN, A .
HUMAN GENE THERAPY, 1995, 6 (10) :1265-1274
[24]   TOLERANCE INDUCED BY INTRATHYMIC INJECTION OF RECOMBINANT ADENOVIRUS IN THE NEONATE [J].
GILGENKRANTZ, H .
M S-MEDECINE SCIENCES, 1995, 11 (10) :1371-1372
[25]  
GRAHAM FL, 1992, VACCINES NEW APPROAC, P363
[26]   PREDNISONE IN DUCHENNE DYSTROPHY - A RANDOMIZED, CONTROLLED TRIAL DEFINING THE TIME COURSE AND DOSE-RESPONSE [J].
GRIGGS, RC ;
MOXLEY, RT ;
MENDELL, JR ;
FENICHEL, GM ;
BROOKE, MH ;
PESTRONK, A ;
MILLER, JP .
ARCHIVES OF NEUROLOGY, 1991, 48 (04) :383-388
[27]   Prevention of immune reactions triggered by first-generation adenoviral vectors by monoclonal antibodies and CTLA4Ig [J].
Guerette, B ;
Vilquin, JT ;
Gingras, M ;
Gravel, C ;
Wood, KJ ;
Tremblay, JP .
HUMAN GENE THERAPY, 1996, 7 (12) :1455-1463
[28]   In vivo expression of full-length human dystrophin from adenoviral vectors deleted of all viral genes [J].
Haecker, SE ;
Stedman, HH ;
BaliceGordon, RJ ;
Smith, DBJ ;
Greelish, JP ;
Mitchell, MA ;
Wells, A ;
Sweeney, HL ;
Wilson, JM .
HUMAN GENE THERAPY, 1996, 7 (15) :1907-1914
[29]   Construction of adenovirus vectors through Cre-lox recombination [J].
Hardy, S ;
Kitamura, M ;
HarrisStansil, T ;
Dai, YM ;
Phipps, ML .
JOURNAL OF VIROLOGY, 1997, 71 (03) :1842-1849
[30]  
Hauser M. A., 1994, American Journal of Human Genetics, V55, pA47