Preclinical drug trials in the mdx mouse: assessment of reliable and sensitive outcome measures.
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. Muscle Nerve, 2008.
Spurney
Christopher F
CF
Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
Gordish-Dressman
Heather
H
Guerron
Alfredo D
AD
Sali
Arpana
A
Pandey
Gouri S
GS
Rawat
Rashmi
R
Van Der Meulen
Jack H
JH
Cha
Hee-Jae
HJ
Pistilli
Emidio E
EE
Partridge
Terence A
TA
Hoffman
Eric P
EP
Nagaraju
Kanneboyina
K
D000367:Age Factors; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography / Q000379:methods; D004576:Electromyography; D005080:Exercise Test / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D053580:Muscle Strength / Q000187:drug effects / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D015203:Reproducibility of Results; D045442:Rotarod Performance Test / Q000379:methods; D012680:Sensitivity and Specificity; D016896:Treatment Outcome