Poloxamer 188 previne a agressão e o remodelamento do músculo cardíaco de cães com distrofia muscular

USA - Poloxamer 188 é um vedante da membrana celular, já anteriormente testado em camundongos. Nest estudo a droga foi administrada por 8 semanas em cães com distrofia muscular. Os cães tratados apresentaram menor fibrose do músculo cardíaco e melhora da função do coração.

O resumo da pesquisa pode ser lida abaixo:

(Circulation, 2009, 120) Abstract 2962: Prevention of Cardiac Injury and Ventricular Remodeling in Dystrophic Dogs by Chronic Administration of Membrane Sealant P188

DeWayne Townsend, IV1; Immanuel Turner1; Soichiro Yasuda1; Joshua Martindale1; Michael S Shillingford1; Joe N Kornegay2; Joseph M Metzger3

1 Univ Minnesota, Minneapolis, MN
2 Univ of North Carolina, Minneapolis, MN
3 Univ Minnesota, Minneapolis, MN

Background: Duchenne muscular dystrophy (DMD) is a fatal disease resulting from the loss of the cytoskeletal protein dystrophin and consequent damage to both skeletal and cardiac muscle cells. In the absence of dystrophin small tears in the cardiac sarcolemma arise causing loss of membrane integrity, muscle wasting, and eventual heart failure in DMD patients. There are no reports of long-term efficacious treatments for dystrophic cardiomyopathy.

Hypothesis: The long term application of the chemical-based membrane sealant Poloxamer 188 (P188) will be safe and effectively slow the development of dystrophic cardiomyopathy.

Methods/Results: Here we show chronic administration of P188 to dystrophin-deficient golden retriever muscular dystrophy (GRMD) dogs in vivo is both safe and effective in blocking the development of cardiac disease. Intravenous administration of 60 mg/kg/hour P188 for 8 weeks in adult GRMD dogs prevented the onset of heart disease observed in saline infused animals. Specifically, significant reductions in fibrotic lesions were observed in P188 infusion (5.8±0.9% of total myocardium) compared to saline infused controls (11.0±1.1%). In saline infused dogs elevations of serum cTnI and BNP were observed. These elevations were not present in P188 infused dogs, indicating a reduction in both myocardial necrosis and congestion in P188 infused dogs. Treatment with P188 also prevented left ventricular dilation that was evident in untreated GRMD control dogs (diastolic volumes: 39±4 vs. 24±3 ml for saline and P188 infused dogs respectively). Regardless of treatment, adult cardiac myocytes isolated from either P188 or saline infused GRMD dogs revealed significantly abnormal passive tension-extension properties. These functional deficits of the isolated myocyte were rapidly reversed upon addition of P188.

Conclusion: Given the clinical prominence of cardiomyopathy and heart failure in DMD, there is an urgent need for effective therapies for the dystrophic heart. This study demonstrates that P188 has the promise of an immediately available therapeutic approach for mitigating the progression of cardiac disease in DMD.

Fonte: http://distrofiamuscular.net/noticias.htm