Correção genética completa das células tronco multipotentes induzidas na distrofia muscular de Duchenne

Japão - o cromossomo humano artificial (HAC) tem vantagens sobre os vetores virais para tratamento das doenças genéticas. Células tronco multipotentes induzidas podem ser úteis para tratamento por serem são retiradas do próprio paciente Nesta pesquisa HAC foi utilizado para corrigir o defeito genético de células tronco multipotentes induzidas do camundongo com distrofia e das células de pacientes com Duchenne. Os resultados demonstraram uma significativa expressão da distrofina nas células tratadas (em torno de 90%). Ou seja a combinação de terapia gênica com células tronco pode ser um caminho para o tratamento da distrofia muscular de Duchenne.

O resumo em inglês pode ser lido abaixo:

(Molecular Therapy 2010;18(2):386–393) Complete Genetic Correction of iPS Cells From Duchenne Muscular Dystrophy

Yasuhiro Kazuki, Masaharu Hiratsuka, Masato Takiguchi, Mitsuhiko Osaki, Naoyo Kajitani, Hidetoshi Hoshiya, Kei Hiramatsu, Toko Yoshino, Kanako Kazuki, Chie Ishihara, Shoko Takehara, Katsumi Higaki, Masato Nakagawa, Kazutoshi Takahashi, Shinya Yamanaka and Mitsuo Oshimura - Japan

Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies.

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