Tratamento prolongado com naproxcinod melhora as alterações cardíacas e musculares em camundongos com distrofia muscular
USA – naproxcinod é um velho anti-inflamatório, o naproxeno, modificado para doar óxido nítrico, um potente vasodilatador. O estudo desta droga por tempo prolongado mostrou aumento da força muscular e melhora da função cardíaca.
O resumo em inglês pode ser lido abaixo:
(Hum. Mol. Genet., Jan 2014) Long-term treatment with naproxcinod significantly improves skeletal and cardiac disease phenotype in the mdx mouse model of dystrophy
Kitipong Uaesoontrachoon, James L. Quinn, Kathleen S. Tatem, Jack H. Van der Meulen, Qing Yu, Aditi Phadke, Brittany K. Miller, Heather Gordish-Dressman, Ennio Ongini, Daniela Miglietta, and Kanneboyina Nagaraju – USA
In Duchenne muscular dystrophy (DMD) patients and the mouse model of DMD, mdx, dystrophin deficiency causes a decrease and mislocalization of muscle-specific neuronal nitric oxide synthase (nNOSμ), leading to functional impairments. Previous studies have shown that nitric oxide (NO) donation associated with anti-inflammatory action has beneficial effects in dystrophic mouse models. In this study, we have systematically investigated the effects of naproxcinod, an NO-donating naproxen derivative, on the skeletal and cardiac disease phenotype in mdx mice. Four-week-old mdx and C57BL/10 mice were treated with four different concentrations (0, 10, 21, and 41 mg/kg) of naproxcinod and 0.9 mg/kg of prednisolone in their food for 9 months. All mice were subjected to twice-weekly treadmill sessions, and functional and behavioral parameters were measured at 3, 6, and 9 months of treatment. In addition, we evaluated in vitro force contraction, optical imaging of inflammation, echocardiography, and blood pressure at the 9-month endpoint prior to sacrifice. We found that naproxcinod treatment at 21 mg/kg resulted in significant improvement in hindlimb grip strength and a 30% decrease in inflammation in the fore- and hindlimbs of mdx mice. Furthermore, we found significant improvement in heart function, as evidenced by improved fraction shortening, ejection fraction, and systolic blood pressure. In addition, the long-term detrimental effects of prednisolone typically seen in mdx skeletal and heart function were not observed at the effective dose of naproxcinod. In conclusion, our results indicate that naproxcinod has significant potential as a safe therapeutic option for the treatment of muscular dystrophies.
