Use of the six-minute walk test to characterize golden retriever muscular dystrophy.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which loss of the dystrophin protein causes progressive skeletal/cardiac muscle degeneration and death within the third decade. For clinical trials and supportive animal studies, DMD disease progression and response to treatment must be established using outcome parameters (biomarkers). The 6-minute walk test (6MWT), defined as the distance an individual can walk in 6 minutes, is commonly used in DMD clinical trials and has been employed in dogs to characterize cardiac and respiratory disease severity. Building on methods established in DMD and canine clinical studies, we assessed the 6MWT in dogs with the DMD genetic homolog, golden retriever muscular dystrophy (GRMD). Twenty-one cross-bred golden retrievers were categorized as affected (DMD mutation and GRMD phenotype), carrier (female heterozygous for DMD mutation and no phenotype), and normal (wild type DMD gene and normal phenotype). When compared to grouped normal/carrier dogs, GRMD dogs walked shorter height-adjusted distances at 6 and 12 months of age and their distances walked declined with age. Percent change in creatine kinase after 6MWT was greater in GRMD versus normal/carrier dogs at 6 months, providing another potential biomarker. While these data generally support use of the 6MWT as a biomarker for preclinical GRMD treatment trials, there were certain limitations. Results of the 6MWT did not correlate with other outcome parameters for GRMD dogs when considered alone and an 80% increase in mean distance walked would be necessary to achieve satisfactory power.
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Austin R
AR
Acosta
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Emiko
E
Van Wie
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
William B
WB
Stoughton
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Amanda K
AK
Bettis
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Heather H
HH
Barnett
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Nicholas R
NR
LaBrie
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Cynthia J
CJ
Balog-Alvarez
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA.
Peter P
PP
Nghiem
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA.
Kevin J
KJ
Cummings
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77843-4458, USA. Electronic address: jkornegay@cvm.tamu.edu.
Joe N
JN
Kornegay
D000375:Aging; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D018450:Disease Progression; D004283:Dog Diseases / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D004285:Dogs; D005260:Female; D006579:Heterozygote; D008297:Male; D009137:Muscular Dystrophy, Animal / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D062706:Prodromal Symptoms; D000070857:Walk Test
D003402:Creatine Kinase
Biomarker; Creatine kinase; Duchenne muscular dystrophy; Golden retriever muscular dystrophy; Six-minute walk test