Epicatequina melhora biogênese mitocondrial, aumenta a distrofina e utrofina, aumenta folistatina enquanto diminui a miostatina, e melhora a resposta ao exercício do músculo esquelético em adultos com distrofia muscular de Becker

USA - A epicatequina foi descoberta para ser uma homóloga estrutural de uma família recém-descoberta de PGC1-alfa ativando hormônios esteróides que promovem biogênese mitocondrial e induzir a regeneração do músculo esquelético. Foi realizado um estudo piloto aberto de epicatequina(50mg duas vezes ao dia por 8 semanas) em adultos ambulatoriais com Distrofia de Becker. A epicatequina induziu biogênese mitocondrial e regeneração muscular. É o único composto oral que pode concomitantemente aumentar a folistatina e diminuir a miostatina. Aumento dos níveis de distrofina e utrofina também foram observados. Houve aumento da força muscular. A epicanterina pode ser uma nova estratégia terapêutica para distrofinopatias. 

O resumo em inglês pode ser lido abaixo:

(MDA Conference, 2015) Epicatechin enhances mitochondrial biogenesis, increases dystrophin and utrophin, increases follistatin while decreasing myostatin, and improves skeletal muscle exercise response in adults with Becker muscular dystrophy (BMD).

Craig M. McDonald, MD1†*, Erik K. Henricson, MPH1†, Bjorn Oskarsson, MD1, Candace Aguilar, BS1, Alina Nicorici, BS1, Nanette Joyce, DO1, Divya Reddy, MD1, Amy Wagner, MS1, Evan deBie, BS1, Erica Goude, BS1, R. Ted Abresch, MS1, Francisco Villareal, MD2, Guy Perkins, MD2, Yetrib Hathout, PhD3, Sundeep Dugar, PhD4, George Schreiner, MD, PhD4. 1University of California, Davis, Sacramento CA; 2University of California, San Diego, San Diego CA; 3Children’s National Medical Center, Washington, DC; 4Cardero Therapeutics, Los Altos Hills, CA.

Objective: To assess the effect of epicatechin on mitochondrial density and muscle function in Becker muscular dystrophy (BMD).
Background: Epicatechin has been discovered to be a structural homologue of a newly discovered family of PGC1-alpha activating steroid hormones that promote mitochondrial biogenesis and induce skeletal muscle regeneration. Epicatechin has been shown to stimulate mitochondrial biogenesis and improve muscle structure and function in the mdx and delta sarcoglycan null models of muscular dystrophy. We conducted an open-label pilot study of epicatechin in ambulatory adults with BMD.
Design: Seven participants received epicatechin 50 mg b.i.d. for 8 weeks. Pre- and post-assessments included: biceps biopsy Western blot and EM, peripheral blood biomarkers, metabolic gas exchange / graded exercise testing, quadriceps tissue saturation index (TSI) by near-infrared spectroscopy, and quantitative muscle strength.
Results: Muscle western blot showed significantly increased dystrophin, utrophin and dysferlin levels. In addition we observed increased muscle follistatin (p=0.002) and decreased myostatin (p=0.008). Increased markers of muscle regeneration included myogenin, Myf5, MyoD, myosin and SkM actin alpha 1 (all p<0.033). Increased proteins associated with mitochondrial growth included PGC1-alpha (p=0.01), AMPK (p=0.004) and mitofilin (p=0.007). Plasma Western blot showed increased follistatin (p=0.0006), decreased myostatin (p=0.04) and increased follistatin:myostatin ratio (p=0.0004). Muscle EM showed increased mitochondrial volume and cristae abundance (p=0.02). Exercise testing demonstrated decreased VO2/kg (p<0.0001), lactate (p<0.0001) and heart rate (p<0.00001) at defined workloads. TSI improved in resting (p<0.008) and post-exercise states (p<0.001). Performance on 6MWT, cycle test maximal watts and strength increased in a subset of patients.
Conclusion: Epicatechin induces mitochondrial biogenesis and muscle regeneration in BMD. It is the only oral compound ever demonstrated to both increase plasma follistatin and decrease plasma myostatin, whose ratio may comprise a future pharmacodynamic biomarker. Increased levels of dystrophin and utrophin suggest that concurrent stimulation of bioenergetics and muscle regeneration may be a novel therapeutic strategy for dystrophinopathies.