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Progress in muscular dystrophy research with special emphasis on gene therapy.

Sugita H, Takeda S - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: Since the disease was described by physicians in the 19th century, information about the subject has been accumulated.Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects.In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping.

View Article: PubMed Central - PubMed

Affiliation: National Center of Neurology and Psychiatry, Tokyo, Japan. sugita@ncnp.go.jp

ABSTRACT
Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping.

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Example of exon skipping therapy for DMD patients with deletion of exon 50. A. Normal dystrophin transcript and mRNA. B. Deletion of exon 50 disrupts the open reading frame, leading to a premature stop codon, unstable mRNA, and a truncated unstable protein. C. Targeted skipping of exon 51 using antisense oligonucleotides, such as AVI-4658 or PRO051 (blue line), restores the reading frame and produces a truncated but functional dystrophin that lacks exons 50 and 51.
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fig02: Example of exon skipping therapy for DMD patients with deletion of exon 50. A. Normal dystrophin transcript and mRNA. B. Deletion of exon 50 disrupts the open reading frame, leading to a premature stop codon, unstable mRNA, and a truncated unstable protein. C. Targeted skipping of exon 51 using antisense oligonucleotides, such as AVI-4658 or PRO051 (blue line), restores the reading frame and produces a truncated but functional dystrophin that lacks exons 50 and 51.

Mentions: Based on the success of AOs-mediated exon skipping in animal models, clinical trials have been performed or are in progress for the skipping of exon 51 of the DMD gene (Fig. 2 and Table 1).


Progress in muscular dystrophy research with special emphasis on gene therapy.

Sugita H, Takeda S - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Example of exon skipping therapy for DMD patients with deletion of exon 50. A. Normal dystrophin transcript and mRNA. B. Deletion of exon 50 disrupts the open reading frame, leading to a premature stop codon, unstable mRNA, and a truncated unstable protein. C. Targeted skipping of exon 51 using antisense oligonucleotides, such as AVI-4658 or PRO051 (blue line), restores the reading frame and produces a truncated but functional dystrophin that lacks exons 50 and 51.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066538&req=5

fig02: Example of exon skipping therapy for DMD patients with deletion of exon 50. A. Normal dystrophin transcript and mRNA. B. Deletion of exon 50 disrupts the open reading frame, leading to a premature stop codon, unstable mRNA, and a truncated unstable protein. C. Targeted skipping of exon 51 using antisense oligonucleotides, such as AVI-4658 or PRO051 (blue line), restores the reading frame and produces a truncated but functional dystrophin that lacks exons 50 and 51.
Mentions: Based on the success of AOs-mediated exon skipping in animal models, clinical trials have been performed or are in progress for the skipping of exon 51 of the DMD gene (Fig. 2 and Table 1).

Bottom Line: Since the disease was described by physicians in the 19th century, information about the subject has been accumulated.Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects.In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping.

View Article: PubMed Central - PubMed

Affiliation: National Center of Neurology and Psychiatry, Tokyo, Japan. sugita@ncnp.go.jp

ABSTRACT
Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping.

Show MeSH
Related in: MedlinePlus