O uso de um peptídeo associado aos oligonucleotídeos melhora o resultado do tratamento de camundongos

USA - os oligonucleotídeos tem sido testados para corrigir o defeito genético nas distrofias musculares; há problemas não solicionados ainda como a necessidade de tratamento de todos os grupos musculares por uma injeção sistêmica. Neste experimento os oligonucleotídeos foram associados a uma cadeia de aminoácidos (peptídeo) e injetados por via sistêmica. Houve uma grande expressão da distrofina em diversos grupos musculares demonstrando que esta forma de tratamento pode ser mais eficiente do que o uso isolado de oligonucleotídeos.

O resumo em inglês pode ser lido abaixo:

(Human Molecular Genetics, 2009) A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice

HaiFang Yin1,2, Hong M. Moulton3, Corinne Betts1, Yiqi Seow1, Jordan Boutilier3, Patrick L. Iverson3 and Matthew J.A. Wood1,*

1 Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK 2 Tianjin Research Centre of Basic Medical Science, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070, China 3 AVI Biopharma Inc., Corvallis, Oregon, 97333, USA

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene that abolish the synthesis of dystrophin protein. Antisense oligonucleotides (AOs) targeted to trigger excision of an exon bearing a mutant premature stop codon in the DMD transcript have been shown to skip the mutated exon and partially restore functional dystrophin protein in dystrophin-deficient mdx mice. To fully exploit the therapeutic potential of this method requires highly efficient systemic AO delivery to multiple muscle groups, to modify the disease process and restore muscle function. While systemic delivery of naked AOs in DMD animal models requires high doses and is of relatively poor efficiency, we and others have recently shown that short arginine-rich peptide-AO conjugates can dramatically improve in vivo DMD splice correction. Here we report for the first time that a chimeric fusion peptide (B-MSP-PMO) consisting of a muscle-targeting heptapeptide (MSP) fused to an arginine-rich cell-penetrating peptide (B-peptide) and conjugated to a morpholino oligomer (PMO) AO directs highly efficient systemic dystrophin splice correction in mdx mice. With very low systemic doses, we demonstrate that B-MSP-PMO restores high-level, uniform dystrophin protein expression in multiple peripheral muscle groups, yielding functional correction and improvement of the mdx dystrophic phenotype. Our data demonstrate proof-of-concept for this chimeric peptide approach in DMD splice correction therapy and is likely to have broad application.

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