O uso de oligonucleotídeos na distrofia miotônica de camundongos

USA - os oligonucleotídeos tem sido testados para reduzir a gravidade das distrofias; utilizando camundongos com distrofia muscular os pesquisadores conseguiram reduzir a expansão de oligonucleotídeos característica da doença; este mesmo tratamento tem sido testado em outros modelos experimentais em camundongos e cães. Há estudos iniciais em seres humanos com distrofia muscular de Duchenne.

O resumo em inglês pode ser lido abaixo:

(Science 17 July 2009: Vol. 325. no. 5938, pp. 336 - 339) Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA

Thurman M. Wheeler, Krzysztof Sobczak, John D. Lueck, Robert J. Osborne, Xiaoyan Lin, Robert T. Dirksen, Charles A. Thornton

Genomic expansions of simple tandem repeats can give rise to toxic RNAs that contain expanded repeats. In myotonic dystrophy, the expression of expanded CUG repeats (CUGexp) causes abnormal regulation of alternative splicing and neuromuscular dysfunction. We used a transgenic mouse model to show that derangements of myotonic dystrophy are reversed by a morpholino antisense oligonucleotide, CAG25, that binds to CUGexp RNA and blocks its interaction with muscleblind-like 1 (MBNL1), a CUGexp-binding protein. CAG25 disperses nuclear foci of CUGexp RNA and reduces the overall burden of this toxic RNA. As MBNL1 is released from sequestration, the defect of alternative splicing regulation is corrected, thereby restoring ion channel function. These findings suggest an alternative use of antisense methods, to inhibit deleterious interactions of proteins with pathogenic RNAs.

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