Duchenne muscular dystrophy
? Annemieke Aartsma-Rus
Overview Â
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Genes and proteins
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Muscles Â
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Muscles Â
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Muscle fibers
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Dystrophin Â
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Genes and proteins
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Gene Protein Cell nucleus DNA Temporary gene copy (RNA) Cell body (cytoplasm)
Protein factory
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Dystrophin  gene Â
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Splicing  2
1
6
3 5
7
4
1
2
3
4
5
6
Annemieke Aartsma-Rus
7
1 2 3 4 5 6 7 8 1 - - - - - - - - - 79
Duchenne: geneHc code disrupted
Annemieke Aartsma-Rus
Duchenne: geneHc code disrupted Exon 46
Exon 47
Annemieke Aartsma-Rus
?
Exon 51
Exon 52
Consequence Â
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Becker: geneHc code maintained
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Becker: geneHc code maintained Exon 46
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Exon 47
Exon 52
Exon 53
Duchenne: no funcHonal dystrophin
Annemieke Aartsma-Rus
No funcHonal dystrophin No dystrophin
Leaky muscle fibers
Calcium leaks into fibers AcHvaHon proteases
Damage energy producing organels
More muscle damage
InflammaHon Scar Hssue
Less muscle regeneraHon
Loss of muscle fibers Loss of muscle func/on Annemieke Aartsma-Rus
Therapy No dystrophin
Leaky muscle fibers
Calcium leaks into fibers AcHvaHon proteases
Damage energy producing organels
More muscle damage
InflammaHon Scar Hssue
Less muscle regeneraHon
Loss of muscle fibers Loss of muscle func/on Annemieke Aartsma-Rus
CorHcosteroids No dystrophin
Leaky muscle fibers
Calcium leaks into fibers AcHvaHon proteases
Damage energy producing organels
More muscle damage
InflammaHon Scar Hssue
Less muscle regeneraHon
Loss of muscle fibers reduced Loss of muscle func/on reduced Annemieke Aartsma-Rus
Reduce muscle fiber damage No dystrophin
Leaky muscle fibers
Calcium leaks into fibers AcHvaHon proteases
Damage energy producing organels
More muscle damage
InflammaHon Scar Hssue
Less muscle regeneraHon
Loss of muscle fibers reduced Loss of muscle func/on reduced Annemieke Aartsma-Rus
Increase muscle mass No dystrophin
Leaky muscle fibers
Loss of muscle fibers compensated Loss of muscle funcHon compensated Annemieke Aartsma-Rus
Utrophin upregulaHon
Annemieke Aartsma-Rus
Utrophin upregulaHon No dystrophin
Leaky muscle fibers
Loss of muscle fibers prevented Loss of muscle func/on prevented Annemieke Aartsma-Rus
Gene therapy No dystrophin
Leaky muscle fibers
Loss of muscle fibers prevented Loss of muscle func/on prevented Annemieke Aartsma-Rus
Cell therapy No dystrophin
Leaky muscle fibers
Loss of muscle fibers prevented Loss of muscle func/on prevented Annemieke Aartsma-Rus
Terms/jargon: cell models
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Terms/jargon: animal models
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Terms/jargon: animal models
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Terms/jargon Â
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Terms/jargon Â
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Terms/jargon Dystrophin immune staining Healthy
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Mdx mouse
Duchenne
Terms/jargon Â
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Terms/jargon Â
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Terms/jargon Â
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Summary/Outlook Â
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More  informaHon Â
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Thank you!
Annemieke Aartsma-Rus