O uso de associação de drogas em camundongos para tratamento da distrofia muscular: estudo experimental com aplicabilidade clínica imdediata

Itália - os autores estudaram a associação de duas drogas conhecidas em camundongos com distrofia por deficiência em α- sarcoglicans; o ibuprofeno é um antinflamatório de uso bastante comum e o dinitrato de isosorbitol é uma medicação vasodilatadora usada no tratamento da angina do peito (uma droga doadora de óxido nítrico). A vantagem de estudar drogas conhecidas é a possibilidade de testes humanos já na fase 3, em pacientes com distrofia, dispensando duas etapas demoradas da pesquisa clínica.

O tratamento combinado foi superior ao observado com cada droga isolada. Houve aumento da capacidade de regeneração, aumento das células precursoras, redução da inflamação e da necrose. Os autores concluem que o ibuprofeno e o dinitrato de isosorbitol tem efeito sinérgico e deveriam ser submetidos a estudos clínicos em pacientes com distrofia muscular.

(British Journal of Pharmacology, 2010) Co-administration of ibuprofen and nitric oxide is an effective experimental therapy for muscular dystrophy, with immediate applicability to humans

Clara Sciorati, Roberta Buono, Emanuele Azzoni, Silvana Casati, Pierangela Ciuffreda, Grazia D'Angelo, Dario Cattaneo, Silvia Brunelli, Emilio Clementi - Italy

Background and purpose: Current therapies for muscular dystrophy are based on corticosteroids. Significant side effects associated with these therapies have prompted several studies aimed at identifying possible alternative strategies. As inflammation and defects of nitric oxide (NO) generation are key pathogenic events in muscular dystrophies, we have studied the effects of combining the NO donor isosorbide dinitrate (ISDN) and the non-steroidal anti-inflammatory drug ibuprofen.

Experimental approach: α-Sarcoglycan null mice were treated for up to 8 months with ISDN (30 mg/kg) plus ibuprofen (50 mg/kg) administered daily in the diet. Effects of ISDN and ibuprofen alone were assessed in parallel. Drug effects on animal motility and muscle function, muscle damage, inflammatory infiltrates and cytokine levels, as well as muscle regeneration including assessment of endogenous stem cell pool, were measured at selected time points.

Key results: Combination of ibuprofen and ISDN stimulated regeneration capacity, of myogenic precursor cells, reduced muscle necrotic damage and inflammation. Muscle function in terms of free voluntary movement and resistance to exercise was maintained throughout the time window analysed. The effects of ISDN and ibuprofen administered separately were transient and significantly lower than those induced by their combination.

Conclusions and implications: Co-administration of NO and ibuprofen provided synergistic beneficial effects in a mouse model of muscular dystrophy, leading to an effective therapy. Our results open the possibility of immediate clinical testing of a combination of ISDN and ibuprofen in dystrophic patients, as both components are approved for use in humans, with a good safety profile.

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