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: 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

A little history…  Pre 21 st 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

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  "Duchenne Muscular Dystrophy: MedlinePlus Medical Encyclopedia." National Library of Medicine - National Institutes of Health. Web. 27 Nov  "Hurdles For Muscular Dystrophy Therapy Cleared." Science Daily: News & Articles in Science, Health, Environment & Technology. Web. 27 Nov  "MDA Research | Utrophin Gene Therapy Benefits DMD Mice." Welcome to MDA | Muscular Dystrophy Association. Web. 27 Nov  "New Muscular Dystrophy Therapy - Biotechnology - an ELab Article at Scientist Live." Scientist Live - the Latest Science News and Opinion. Web. 27 Nov  Van Deutekom, Judith C.T, and Gert-Jan B. Van Ommen. "Advances in Duchenee Muscular Dystrophy Gene Therapy." Web. 27 Nov