Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle.
 ...
PMID:Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. 843 25

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder which is caused by a defect of dystrophin, a 427-kDa muscle cell membrane protein. One of the possible means of DMD therapy is to express the dystrophin gene in patients' muscles. In this study, full length dystrophin cDNA was expressed in mdx (muscular dystrophy model) mouse muscle using the hemagglutinating virus of Japan (HVJ)-liposome method. With the HVJ-liposome method, the lacZ reporter genes were expressed in 50-80% of cultured mdx mouse myoblasts, which suggested its potential usefulness for an in vivo gene study. Three expression vectors containing human full length dystrophin cDNA driven by Rous sarcoma virus (RSV), mouse leukemia virus, or human dystrophin promoters, were used. HVJ-liposomes containing these plasmids were directly injected into mdx mouse quadriceps muscle. The highest efficiency of expression of dystrophin was in 26% of the muscle fibers at the injected site on day 3 after HVJ-liposome injection of the RSV-based vector. The expression was decreased on day 10. The study thus demonstrates the feasibility of full length human dystrophin cDNA transfer and dystrophin expression using HVJ-liposomes in vivo.
 ...
PMID:Expression of full-length human dystrophin cDNA in mdx mouse muscle by HVJ-liposome injection. 878 5

The muscular dystrophies are a group of devastating genetic disorders that affect both skeletal and cardiac muscle. An effective gene therapy for these diseases requires bodywide muscle delivery. Tyrosine mutant adeno-associated virus (AAV) has been considered as a class of highly potent gene transfer vectors. Here, we tested the hypothesis that systemic delivery of tyrosine mutant AAV can result in bodywide muscle transduction in newborn dogs. Three tyrosine mutant AAV vectors (Y445F/Y731F AAV-1, Y445F AAV-6, and Y731F AAV-9) were evaluated. These vectors expressed the alkaline phosphatase reporter gene under transcriptional regulation of either the muscle-specific Spc5-12 promoter or the ubiquitous Rous sarcoma virus promoter. Robust skeletal and cardiac muscle transduction was achieved with Y445F/Y731F AAV-1. However, Y731F AAV-9 only transduced skeletal muscle. Surprisingly, Y445F AAV-6 resulted in minimal muscle transduction. Serological study suggests that the preexisting neutralization antibody may underlie the limited transduction of Y445F AAV-6. In summary, we have identified Y445F/Y731F AAV-1 as a potentially excellent systemic gene transfer vehicle to target both skeletal muscle and the heart in neonatal puppies. Our findings have important implications in exploring systemic neonatal gene therapy in canine models of muscular dystrophy.
 ...
PMID:Systemic gene transfer reveals distinctive muscle transduction profile of tyrosine mutant AAV-1, -6, and -9 in neonatal dogs. 2510 53