Novos estudos para correção da proteína CFTR
Autor: Mauro Ferreira | Publicado: 2013-01-22T12:16:00-02:00

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O sucesso de ivacaftor direcionado ao defeito CFTR na FC tem
chamdo a atenção para outros agentes que podem potenciar ou corrigir a função &nbsp;do CFTR. Entre os candidatos estão os
inibidores da fosfodiesterase-5 (PDE-5), como o sildenafil (Viagra), vardenafil
(Levitra) e taladafil (Cialis).





Um estudo inicial relatou que o sildenafil aumentou o
tráfico de CFTR para a membrana apical de células epiteliais nasais em
pacientes com FC (Dormer et al Thorax 2005;. 60:55-9; texto completo no site
www.ncbi.nlm.nih.gov/pmc/articles/PMC1747155/pdf/v060p00055.pdf ). Dois estudos
com animais que verificaram que os inibidores de PDE-5 administrado quer por
injeção intraperitoneal ou nebulização foram capazes de estimular o transporte
de cloreto, como mostrado por alterações na diferença de potencial nasal (NPD)
(Lubamba et al Am J Respir Crit Care Med 2008;. 177:506 -515, texto completo em
http://ajrccm.atsjournals.org/content/177/5/506.full.pdf+html;. Lubamba Eur
Respir et al J 2011; 37:72-78).



Um recente estudo alemão descobriu também que sildenafil atua
como um potenciador e corretor da atividade do canal CFTR de deltaF508,
contudo, as doses elevadas requeridas pode não ser adequadas para o tratamento
da FC (Leier et ai Cell Physiol Biochem 2012.; 29:775-790).



Uma nova revisão de inibidores de PDE-5 sugere que
vardenafil inalado pode ser mais apropriado, devido à sua potência e maior
duração de ação (Noel et al Frente Pharmacol 2012;. 3:167; texto completo em
www.ncbi.nlm.nih. gov/pmc/articles/PMC3444771/pdf/fphar-03-00167.pdf). Inalação
teve um início de ação mais rápido, pareceu bem tolerada e não foi associada a
alterações clinicamente significativas na frequência cardíaca ou pressão
arterial na fase I de testes (Berry et al J Sex Med. 2009;. Epublished 28 de
julho de 2009). Dados preliminares sugerem que vardenafil também reduz a
expressão das citocinas inflamatórias no fluido broncoalveolar (Lubamba et al J
Cisto Fibros 2012;. 11:266-273), mas são precisos mais estudos.


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