Transcript Duchenne Muscular Dystrophy and Utrophin

Duchenne
Muscular
Dystrophy and
Utrophin
Iona Ross
BME 281
November 29, 2011
About DMD
1
out of every 3500 male infants
 One of the 9 types – most common
 Rapid weakening of muscles
 Mental retardation/ poor motor skills
 Life expectancy: 20-30 yrs.
 Mutant gene for dystrophin – protein
Internal Muscular Differences
 Left
– normal
 Middle – DMD
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Loss of exons
mRNA translates what
it can
Missing exons lead to
frameshift/translation
error – lack of
dystrophin/protein
http://www.childrensnational.org/research/OurResearch/TranslationalResearch/CGMR/MuscularDystrophy.aspx
A little history…
 Pre

21st century – inject more dystrophin?
Mice testing – rejected by immune system
 2003
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– 3 main processes to treat DMD
I focused on injection of utrophin
Why utrophin?
 Structurally
and functionally very similar –
both proteins, hold muscle tissue together
 “Well-known” by the body

Body tissues and muscles
 As
fetus – dispersed over much of the muscle
 Toddler – gradually replaced by dystrophin
 Once mature – neuromuscular/myotendinous
junctions

Widely effective
Healthy dystrophin genes

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Top – most common
Middle – results of lab
mice testing
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<http://duchenne.plant.nl/media/doc/nrg1003.pdf>
Red N-terminal and
yellow dystrophin
portion – not essential
Green cysteine-rich
region – v. important
Blue C-terminal – can be
shorter; correct patterns
are important
Bottom – utrophin gene
Utrophin tests
 Prior
to 2008 – utrophin injected into
muscles of mice; widespread effect
 October 2008 – scientists at Univ. of
Minnesota
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
Injected utrophin into leg muscles of dog
Widespread effect
Only nine times smaller than a human!
Future
 Short-term


Human testing
Pill that administers utrophin at regular
intervals
 Long-term


Cure!
Already talk of altering genes at birth
before utrophin is taken over by dystrophin
References
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"Duchenne Muscular Dystrophy (DMD) - Welcome to MDA, Helping Jerry's
Kids." Welcome to MDA | Muscular Dystrophy Association. Web. 27 Nov. 2011.
<http://www.mda.org/disease/dmd.html>.
"Duchenne Muscular Dystrophy: MedlinePlus Medical Encyclopedia." National
Library of Medicine - National Institutes of Health. Web. 27 Nov. 2011.
<http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm>.
"Hurdles For Muscular Dystrophy Therapy Cleared." Science Daily: News &
Articles in Science, Health, Environment & Technology. Web. 27 Nov. 2011.
<http://www.sciencedaily.com/releases/2008/10/081029104313.htm>.
"MDA Research | Utrophin Gene Therapy Benefits DMD Mice." Welcome to
MDA | Muscular Dystrophy Association. Web. 27 Nov. 2011.
<http://www.mdausa.org/research/070817dmd-mice-utrophin.html>.
"New Muscular Dystrophy Therapy - Biotechnology - an ELab Article at
Scientist Live." Scientist Live - the Latest Science News and Opinion. Web. 27
Nov. 2011. <http://www.scientistlive.com/European-ScienceNews/Biotechnology/New_muscular_dystrophy_therapy/22466/>.
Van Deutekom, Judith C.T, and Gert-Jan B. Van Ommen. "Advances in
Duchenee Muscular Dystrophy Gene Therapy." Web. 27 Nov. 2011.
<http://duchenne.plant.nl/media/doc/nrg1003.pdf>.