FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W134696546> ?p ?o ?g. }

• W134696546 abstract "Duchenne muscular dystrophy (DMD) is a fatal genetic disorder caused by mutations in the gene coding for dystrophin protein, which give rise to a dysfunctional protein in skeletal muscle. Dystrophic muscle progressively degenerates. In addition, necrotic muscle fibers undergo high levels of inflammation that in turn promote the pathology that is associated with this devastating disease. Therefore, treatments that 1) restore expression a functional dystrophin protein in dystrophic muscles, and 2) lower the ongoing inflammation in the necrotic muscle tissue, are both important in ameliorating DMD phenotype. Transfer of a functional dystrophin gene using a viral vector can help restore the missing dystrophin protein in dystrophic muscles. The host immune system, however, is a major barrier to successful vector-mediated dystrophin protein expression in a dystrophic host, as anti-dystrophin immune response leads to rejection of the protein. Here I show that temporal elimination of the host immune system by irradiation in the mdx mouse, a murine model of DMD, prior to vector-mediated dystrophin gene delivery, leads to a delayed and diminished host anti-dystrophin immune response. These findings are important for a better evaluation of anti-dystrophin immunity in a dystrophic host. In the case of lowering inflammation in dystrophic muscles, I investigated the effects of rapamycin, a potent immunosuppressant, on both dystrophic phenotype and dystrophin gene transfer in mdx mice. Treatment of adult mdx muscles with rapamycin lead to significantly lower levels of muscle fiber necrosis and reduced effector T cell infiltration in dystrophic muscles. These events correlated with a difference in activation of the mammalian target of rapamycin (mTOR) in the diaphragm muscle, but not the TA muscle, suggesting a differential regulation of mTOR activation in the two tissues. Rapamycin treatment, however, did not allow for a higher level of vector-mediated dystrophin protein expression in treated muscles. In general, these findings shed more light on the effects of manipulating the immune system in a dystrophic host in terms of both reducing the inflammation that is associated with DMD and reducing anti-dystrophin responses following gene therapy, suggesting that regulation of the immune system is essential in ameliorating DMD." @default.
• W134696546 created "2016-06-24" @default.
• W134696546 creator A5034659478 @default.
• W134696546 date "2010-12-15" @default.
• W134696546 modified "2023-09-27" @default.
• W134696546 title "Effects of manipulating the immune system on dystrophin gene transfer and dystrophic phenotype in striated muscles of Duchenne muscular dystrophy model, mdx mouse" @default.
• W134696546 cites W139352560 @default.
• W134696546 cites W1487550568 @default.
• W134696546 cites W1495989427 @default.
• W134696546 cites W1515471616 @default.
• W134696546 cites W1530473805 @default.
• W134696546 cites W153509890 @default.
• W134696546 cites W153537846 @default.
• W134696546 cites W1561279073 @default.
• W134696546 cites W1565841551 @default.
• W134696546 cites W1575585006 @default.
• W134696546 cites W1579538128 @default.
• W134696546 cites W1582679620 @default.
• W134696546 cites W1586159393 @default.
• W134696546 cites W1626962603 @default.
• W134696546 cites W1661658508 @default.
• W134696546 cites W1671914626 @default.
• W134696546 cites W1682559160 @default.
• W134696546 cites W1766033193 @default.
• W134696546 cites W1786058540 @default.
• W134696546 cites W1808026750 @default.
• W134696546 cites W1820144832 @default.
• W134696546 cites W1839872679 @default.
• W134696546 cites W1878849363 @default.
• W134696546 cites W1918052238 @default.
• W134696546 cites W1942870285 @default.
• W134696546 cites W1964924515 @default.
• W134696546 cites W1965355806 @default.
• W134696546 cites W1966119850 @default.
• W134696546 cites W1974703394 @default.
• W134696546 cites W1975678510 @default.
• W134696546 cites W1976323848 @default.
• W134696546 cites W1977214541 @default.
• W134696546 cites W1978376203 @default.
• W134696546 cites W1978583778 @default.
• W134696546 cites W1978757676 @default.
• W134696546 cites W1984909066 @default.
• W134696546 cites W1986088843 @default.
• W134696546 cites W1986851889 @default.
• W134696546 cites W1987259015 @default.
• W134696546 cites W1988248063 @default.
• W134696546 cites W1988474688 @default.
• W134696546 cites W1988637973 @default.
• W134696546 cites W1989641304 @default.
• W134696546 cites W1990561446 @default.
• W134696546 cites W1990748900 @default.
• W134696546 cites W1991344211 @default.
• W134696546 cites W1992117911 @default.
• W134696546 cites W1995515336 @default.
• W134696546 cites W1998249081 @default.
• W134696546 cites W1999113624 @default.
• W134696546 cites W1999875730 @default.
• W134696546 cites W2000553115 @default.
• W134696546 cites W2000650296 @default.
• W134696546 cites W2002981816 @default.
• W134696546 cites W2005402291 @default.
• W134696546 cites W2007497663 @default.
• W134696546 cites W2008686731 @default.
• W134696546 cites W2010665897 @default.
• W134696546 cites W2013643860 @default.
• W134696546 cites W2019954087 @default.
• W134696546 cites W2020217527 @default.
• W134696546 cites W2021455330 @default.
• W134696546 cites W2023669482 @default.
• W134696546 cites W2026147568 @default.
• W134696546 cites W2026590936 @default.
• W134696546 cites W2026975258 @default.
• W134696546 cites W2027588464 @default.
• W134696546 cites W2027754833 @default.
• W134696546 cites W2028273824 @default.
• W134696546 cites W2028695000 @default.
• W134696546 cites W2029242980 @default.
• W134696546 cites W2029286854 @default.
• W134696546 cites W2034309480 @default.
• W134696546 cites W2036877355 @default.
• W134696546 cites W2037243869 @default.
• W134696546 cites W2037606228 @default.
• W134696546 cites W2038009703 @default.
• W134696546 cites W2043998532 @default.
• W134696546 cites W2044197648 @default.
• W134696546 cites W2044351877 @default.
• W134696546 cites W2044962040 @default.
• W134696546 cites W2046323838 @default.
• W134696546 cites W2046669029 @default.
• W134696546 cites W2047503966 @default.
• W134696546 cites W2047988806 @default.
• W134696546 cites W2048376025 @default.
• W134696546 cites W2049592320 @default.
• W134696546 cites W2050388013 @default.
• W134696546 cites W2051967937 @default.
• W134696546 cites W2052131992 @default.
• W134696546 cites W2052194461 @default.
• W134696546 cites W2054929937 @default.
• W134696546 cites W2055687053 @default.
• W134696546 cites W2059377172 @default.

• next