1. Research and Development Name: Julie Long Student Number: C12307761 Course Code: DT204.2

2. Disease: Becker Muscular Dystrophy

3. What? Becker Muscular Dystrophy is an inherited disorder mostly found in boys. (X-linked) It involves muscle weakening especially of the legs and pelvis Similar to Duchenne Muscular Dystrophy.

4. X-Linked recessive inherited disorder mutation in dystrophin gene which is the largest gene in the human genome and is prone to mutation.

5. Mutation in the gene that produces dystrophin. (Genetic or spontaneous) This protein keeps skeletal and cardiac muscle cells intact by stabilising and protecting muscle fibres.

6. CK (creatine kinase) blood test and biopsy as a first round test. Western blotting- males Immunofluorescene - females DNA analysis by PCR and southern blotting.

7. Western Blotting Immunofluorescene Lanes 1, 3, 5 and 7 are normal controls but lanes 2, 4 and 6 show abnormal or absent dystrophin. Lanes 4 and 6 show BMD as abnormal dystrophin is displayed. Negative fibres are interspersed amoung positive ones which indicates a carrier.

8. A study done in the United States in 2007 showed an estimated 1 of every 5,600 to 7,700 males from 5 to 24 years of age had BDM. 500-600 newborns are diagnosed with muscular dystrophy each year in the USA. In 2003 the cumulative birth incidence in north England was at least 1 in every 18,450 males.

9. No known cure available. Treatments to control symptoms and maximise the standard of life. Activity and physical exercise increase muscle strength. Research into oral albuterol.

10. Addresses the functional need of the patient as the disease progresses, includes exercises and stretching tight muscle. The patient is also thought techniques for energy conservation, joint protection, and the prevention of overuse fatigue. Specific adaptions are provided where needed to enable individuals to maintain functional motility and independence in everyday life. As muscles weaken towards the end of the disease there is an increased risk of aspiration pneumonia and may lead to dysphagia. Dysphagia concerns may be evaluated by a speech therapist.

11. Best treatment currently available. Prednisone and deflazacort. Improve muscle strength and function Prolong respiratory/ cardiac dysfunction. Caution must be taken due to side effects such as weight gain, hair growth, hyperactivity and reduced bone density.

12. Exon skipping is being investigated as a therapy to restore the reading frame of the dystrophin gene. Proven to be successful in mice. Multi-exon skipping therapy strategy is being investigated in dogs as well as mice.

14. Premature Stop codons prevent cell from completely assembling dystrophin. Causes BMD and DMD. A drug such as ataluren enables the cell the “read through” this stop codon.

15. Utrophin resembles dystrophin. It is produced normally and is fully functional in BMB. Therefore unlikely to produce an immune response. Injection of modified utrophin or suppression of utrophin production inhibitor.

16. References Genetic home reference, Duchenne and Becker Muscular dystrophy, Reviewed feb 2012. Available from: http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular- dystrophy http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular- dystrophy Julie Roddick, Becker Muscular Dystrophy, Published Aug 2012. Available from http://www.healthline.com/health/beckers-muscular- dystrophy#Overview,http://www.healthline.com/health/beckers-muscular- dystrophy#Overview Beggs A.H., Kunkel L.M. Improved diagnosis of Duchenne/Becker muscular dystrophy. J. Clin. Invest. 1990;85(3):613–619 Bonifati MD, Ruzza G, Bonometto P, Berardinelli A,Et al. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve. 2000;23:1344–1347. doi: 10.1002/1097-4598(200009)23:9 3.3.CO;2-6

17. Touznik A, Lee JJ, Yokota T, New Developments in exon skipping and splice modulation therapies for neuromuscular diseases.Expert Opin Biol Ther. 2014 Mar 12. Wilton SD, Fletcher S. Splice Modification to Restore Functional Dystrophin Synthesis in Duchenne Muscular Dystrophy. Curr Pharm Des 2010. 2009;16(8):988–1001. Bushby KM, Thambyayah M, Gardner-Medwin D. Prevalence and incidence of Becker muscular dystrophy, Lancet. 1991 Apr 27;337(8748):1022-4. Mandac B, Becker muscular treatment and management. Available from: http://emedicine.medscape.com/article/313417-treatment#a1129