Duchenne Muscular Dystrophy and UtrophinIona RossBME 281November 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

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 – 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 Top – most common Middle – results of lab

mice testing 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<http://duchenne.plant.nl/media/doc/nrg1003.pdf>

Utrophin tests Prior to 2008 – utrophin injected into

muscles of mice; widespread effect October 2008 – scientists at Univ. of

Minnesota 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 "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-Science-News/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>.