PRECLINICAL DRUG TRIALS IN THE mdx MOUSE: ASSESSMENT OF RELIABLE AND SENSITIVE OUTCOME MEASURES

被引：127

作者：

Spurney, Christopher F. ^{[1
]}

Gordish-Dressman, Heather ^{[1
]}

Guerron, Alfredo D. ^{[1
]}

Sali, Arpana ^{[1
]}

Pandey, Gouri S. ^{[1
]}

Rawat, Rashmi ^{[1
]}

Van Der Meulen, Jack H. ^{[1
]}

Cha, Hee-Jae ^{[1
]}

Pistilli, Emidio E. ^{[1
]}

Partridge, Terence A. ^{[1
]}

Hoffman, Eric P. ^{[1
]}

Nagaraju, Kanneboyina ^{[1
]}

机构：

[1] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA

来源：

MUSCLE & NERVE | 2009年 / 39卷 / 05期

关键词：

Duchenne muscular dystrophy; mdx mouse; preclinical trials; statistical analysis; phenotyping; muscle function tests; exercise; echocardiography; DUCHENNE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; DIAPHRAGM MUSCLE; IN-VIVO; VOLUNTARY EXERCISE; MICE LACKING; IMPROVES; MODEL; STRENGTH; GENE;

D O I：

10.1002/mus.21211

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The availability of animal models for Duchenne muscular dystrophy has led to extensive preclinical research on potential therapeutics. Few studies have focused on reliability and sensitivity of endpoints for mdx mouse drug trials. Therefore, we sought to compare a wide variety of reported and novel endpoint measures in exercised mdx and normal control mice at 10, 20, and 40 weeks of age. Statistical analysis as well as power calculations for expected effect sizes in mdx preclinical drug trials across different ages showed that body weight, normalized grip strength, horizontal activity, rest time, cardiac function measurements, blood pressure, total central/peripheral nuclei per fiber, and serum creatine kinase are the most effective measurements for detecting drug-induced changes. These data provide an experimental basis upon which standardization of preclinical drug testing can be developed.

引用

页码：591 / 602

页数：12

共 48 条

[31] Defect in microvascular adaptation to chronic changes in blood flow in mice lacking the gene encoding for dystrophin [J].

Loufrani, L ;

Levy, BI ;

Henrion, D .

CIRCULATION RESEARCH, 2002, 91 (12) :1183-1189

[32] Flow (shear stress)-induced endothelium-dependent dilation is altered in mice lacking the gene encoding for dystrophin [J].

Loufrani, L ;

Matrougui, K ;

Gorny, D ;

Duriez, M ;

Blanc, I ;

Lévy, BI ;

Henrion, D .

CIRCULATION, 2001, 103 (06) :864-870

[33] Disodium cromoglycate protects dystrophin-deficient muscle fibers from leakiness [J].

Marques, Maria Julia ;

Machado, Rafael Ventura ;

Minatel, Elaine ;

Neto, Humberto Santo .

MUSCLE & NERVE, 2008, 37 (01) :61-67

[34] Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies [J].

Nagaraju, K ;

Raben, N ;

Loeffler, L ;

Parker, T ;

Rochon, PJ ;

Lee, E ;

Danning, C ;

Wada, R ;

Thompson, C ;

Bahtiyar, G ;

Craft, J ;

van Huijsduijnen, RH ;

Plotz, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (16) :9209-9214

[35] Nutritional therapy improves function and complements corticosteroid intervention in mdx mice [J].

Payne, ET ;

Yasuda, N ;

Bourgeois, JM ;

Devries, MC ;

Rodriguez, MC ;

Yousuf, J ;

Tarnopolsky, MA .

MUSCLE & NERVE, 2006, 33 (01) :66-77

[36] Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis [J].

Petrella, John K. ;

Kim, Jeong-Su ;

Mayhew, David L. ;

Cross, James M. ;

Bamman, Marcas M. .

JOURNAL OF APPLIED PHYSIOLOGY, 2008, 104 (06) :1736-1742

[37] Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings [J].

Quinlan, JG ;

Hahn, HS ;

Wong, BL ;

Lorenz, JN ;

Wenisch, AS ;

Levin, LS .

NEUROMUSCULAR DISORDERS, 2004, 14 (8-9) :491-496

[38] Modulation of disease severity in mice with targeted disruption of the acid α-glucosidase gene [J].

Raben, N ;

Nagaraju, K ;

Lee, E ;

Plotz, P .

NEUROMUSCULAR DISORDERS, 2000, 10 (4-5) :283-291

[39] Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice [J].

Radley, Hannah G. ;

Grounds, Miranda D. .

NEUROBIOLOGY OF DISEASE, 2006, 23 (02) :387-397

[40]

ROSENBERG RN, MOL GENETIC BASIS NE

← 1 2 3 4 5 →