Beta-hydroxy-beta-methylbutyrate (HMB) improves daily activity and whole body protein metabolism in Duchenne Muscular Dystrophy Dogs

Topic:

Translational Research

Poster Number: P151

Author(s):

Macie Mackey, BA, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, Alexis Rutledge, Texas A&M University, Kyle Tehas, Texas A&M University, Corine Kaderli, Texas A&M University, Meredith Poling, Texas A&M University, Sidney Arnim, Texas A&M University, Vitaliy Dernov, Texas A&M University, Celine van Sas, Center for Translational Research in Aging and Longevity Texas A&M University, Gabriella A.M. ten Have, PhD, Center for Translational Research in Aging and Longevity Texas A&M University, Marielle P.K.J. Engelen, PhD, Center for Translational Research in Aging and Longevity Texas A&M University, Nicolaas Deutz, MD, PhD, Department of Health and Kinesiology, Texas A&M University, Peter Nghiem, DVM, PhD, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University

Introduction
Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease due to loss of dystrophin, leading to progressive muscle wasting and physical inactivity. We studied the effect of daily supplementation of the anabolic substrate beta-hydroxy-beta-methylbutyrate (HMB) on whole body protein and amino acid kinetics using novel isotope methods and daily activity in a canine model of DMD.
Methods
Six DMD dogs were administered 3 grams daily of HMB or placebo for 28 days according to a randomized, placebo-controlled, double-blinded crossover design. We measured pre- and post-intervention daily activity, biochemistry markers, and whole body amino acid kinetics. We tracked daily activity with an activity monitoring device and measured plasma creatine kinase and standard clinical biochemistry panels to monitor muscle and organ function. To calculate whole body and intracellular amino acid production, we administered in the postabsorptive state an IV stable isotope solution containing 18 amino acid tracers. We collected blood before and six times after until two hours post tracer pulse administration and measured amino acid enrichments and concentrations by LC-MS/MS, subsequently followed by (non) compartmental modeling of the decay enrichment curves. Results were expressed as mean with 95% CI.
Results
Whole body production of various amino acids, specifically hydroxyproline (marker of collagen breakdown), were attenuated in HMB-dosed DMD dogs. DMD dogs treated with HMB as compared to placebo had a respective 40% increase in exertional (play) (951 [827.3, 1075] versus 568.8[490.8, 646.9]; p<0.0001) and 10.5% increase in non-exertional (active) activity (15,366 [14742, 15990] versus 13,806 [13148,14466]; p=0.0016). In addition, a 6% reduction was found in rest time after HMB supplementation compared to placebo (23,857 [23,130, 24,584], versus 25,363 [24500, 26225]; p=0.0122). Creatine kinase was reduced in HMB compared to placebo, but statistically was not significant. We did not observe any adverse clinical or biochemical-related effects of HMB dosing. Conclusion Daily HMB supplementation in DMD dogs is able to positively influence protein and amino acid metabolism and improve overall daily activity.