Gene therapy for muscular dystrophy: Lessons learned and path forward

Neuroscience Letters

Volumn 527, Issue 2, 2012, Pages 90-99

  Mendell, Jerry R ^a   Rodino Klapac, Louise ^a   Sahenk, Zarife ^a   Malik, Vinod ^a   Kaspar, Brian K ^a   Walker, Christopher M ^a   Clark, K Reed ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

Adeno associated virus; Alpha sarcoglycan; Dystrophin; Exon skipping; Follistatin; Mutation suppression

Indexed keywords

ALPHA SARCOGLYCAN; ATALUREN; DEFLAZACORT; DRISAPERSEN; DYSTROPHIN; ETEPLIRSEN; FOLLISTATIN; FS 344; GAMMA INTERFERON; GAMMA SARCOGLYCAN; GENTAMICIN; METHYLPREDNISOLONE; MYOSTATIN; PARVOVIRUS VECTOR; PLACEBO; PREDNISONE; UNCLASSIFIED DRUG;

ADENO ASSOCIATED VIRUS; BECKER MUSCULAR DYSTROPHY; DOUBLE BLIND PROCEDURE; DRUG APPROVAL; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DUCHENNE MUSCULAR DYSTROPHY; ELECTROMYOGRAPHY; EMERY DREIFUSS MUSCULAR DYSTROPHY; EXON SKIPPING; FOOD AND DRUG ADMINISTRATION; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE THERAPY; HUMAN; INCLUSION BODY MYOSITIS; LIMB GIRDLE MUSCULAR DYSTROPHY; LONG TERM CARE; MUSCLE BIOPSY; MUSCLE STRENGTH; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OPEN READING FRAME; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; QUADRICEPS FEMORIS MUSCLE; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW;

CLINICAL TRIALS AS TOPIC; CODON, TERMINATOR; CREATINE KINASE; DEPENDOVIRUS; DYSTROPHIN; EXONS; FOLLISTATIN; GENETIC THERAPY; GENETIC VECTORS; HUMANS; MUSCULAR DYSTROPHIES; MUSCULAR DYSTROPHY, DUCHENNE; MUTATION; MYOSITIS, INCLUSION BODY; OXADIAZOLES; PROMOTER REGIONS, GENETIC; RNA PRECURSORS; SARCOGLYCANS;

EID: 84866762773     PISSN: 03043940     EISSN: 18727972     Source Type: Journal    
DOI: 10.1016/j.neulet.2012.04.078     Document Type: Review

References (48)

1. Barton-Davis E.R., Cordier L., Shoturma D.I., Leland S.E., Sweeney H.L. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. Journal of Clinical Investigation 1999, 104:375-381.
2. Biggar W.D., Harris V.A., Eliasoph L., Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscular Disorders 2006, 16:249-255.
3. Brooke M.H., Fenichel G.M., Griggs R.C., Mendell J.R., Moxley R., Miller J.P., Province M.A. Clinical investigation in Duchenne dystrophy: 2. Determination of the power of therapeutic trials based on the natural history. Muscle and Nerve 1983, 6:91-103.
4. Chen J.Y., Clark M.J. Family function in families of children with Duchenne muscular dystrophy. Family and Community Health 2007, 30:296-304.
5. Cirak S., Arechavala-Gomeza V., Guglieri M., Feng L., Torelli S., Anthony K., Abbs S., Garralda M.E., Bourke J., Wells D.J., Dickson G., Wood M.J., Wilton S.D., Straub V., Kole R., Shrewsbury S.B., Sewry C., Morgan J.E., Bushby K., Muntoni F. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 2011, 378:595-605.
6. England S.B., Nicholson L.V., Johnson M.A., Forrest S.M., Love D.R., Zubrzycka-Gaarn E.E., Bulman D.E., Harris J.B., Davies K.E. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 1990, 343:180-182.
7. Escolar D.M., Hache L.P., Clemens P.R., Cnaan A., McDonald C.M., Viswanathan V., Kornberg A.J., Bertorini T.E., Nevo Y., Lotze T., Pestronk A., Ryan M.M., Monasterio E., Day J.W., Zimmerman A., Arrieta A., Henricson E., Mayhew J., Florence J., Hu F., Connolly A.M. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology 2011, 77:444-452.
8. Fan Z., Kocis K., Valley R., Howard J.F., Chopra M., An H., Lin W., Muenzer J., Powers W. Safety and feasibility of high-pressure transvenous limb perfusion with 0.9% saline in human muscular dystrophy. Molecular Therapy 2012, 20:456-461.
9. Flanigan K.M., von Niederhausern A., Dunn D.M., Alder J., Mendell J.R., Weiss R.B. Rapid direct sequence analysis of the dystrophin gene. American Journal of Human Genetics 2003, 72:931-939.
10. Goemans N.M., Tulinius M., van den Akker J.T., Burm B.E., Ekhart P.F., Heuvelmans N., Holling T., Janson A.A., Platenburg G.J., Sipkens J.A., Sitsen J.M., Aartsma-Rus A., van Ommen G.J., Buyse G., Darin N., Verschuuren J.J., Campion G.V., de Kimpe S.J., van Deutekom J.C. Systemic administration of PRO051 in Duchenne's muscular dystrophy. New England Journal of Medicine 2011, 364:1513-1522.
11. Goyenvalle A., Babbs A., Powell D., Kole R., Fletcher S., Wilton S.D., Davies K.E. Prevention of dystrophic pathology in severely affected dystrophin/utrophin-deficient mice by morpholino-oligomer-mediated exon-skipping. Molecular Therapy 2010, 18:198-205.
12. Haidet A.M., Rizo L., Handy C., Umapathi P., Eagle A., Shilling C., Boue D., Martin P.T., Sahenk Z., Mendell J.R., Kaspar B.K. Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:4318-4322.
13. Harper S.Q., Hauser M.A., DelloRusso C., Duan D., Crawford R.W., Phelps S.F., Harper H.A., Robinson A.S., Engelhardt J.F., Brooks S.V., Chamberlain J.S. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nature medicine 2002, 8:253-261.
14. Herson S., Hentati F., Rigolet A., Behin A., Romero N.B., Leturcq F., Laforet P., Maisonobe T., Amouri R., Haddad H., Audit M., Montus M., Masurier C., Gjata B., Georger C., Cherai M., Carlier P., Hogrel J.Y., Herson A., Allenbach Y., Lemoine F.M., Klatzmann D., Sweeney H.L., Mulligan R.C., Eymard B., Caizergues D., Voit T., Benveniste O. A phase I trial of adeno-associated virus serotype 1-gamma-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C. Brain 2012, 135:483-492.
15. Hirawat S., Welch E.M., Elfring G.L., Northcutt V.J., Paushkin S., Hwang S., Leonard E.M., Almstead N.G., Ju W., Peltz S.W., Miller L.L. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. Journal of Clinical Pharmacology 2007, 47:430-444.
16. Kinali M., Arechavala-Gomeza V., Feng L., Cirak S., Hunt D., Adkin C., Guglieri M., Ashton E., Abbs S., Nihoyannopoulos P., Garralda M.E., Rutherford M., McCulley C., Popplewell L., Graham I.R., Dickson G., Wood M.J., Wells D.J., Wilton S.D., Kole R., Straub V., Bushby K., Sewry C., Morgan J.E., Muntoni F. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurology 2009, 8:918-928.
17. Koenig M., Hoffman E.P., Bertelson C.J., Monaco A.P., Feener C., Kunkel L.M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987, 50:509-517.
18. Koenig M., Monaco A.P., Kunkel L.M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 1988, 53:219-228.
19. Kota J., Handy C.R., Haidet A.M., Montgomery C.L., Eagle A., Rodino-Klapac L.R., Tucker D., Shilling C.J., Therlfall W.R., Walker C.M., Weisbrode S.E., Janssen P.M., Clark K.R., Sahenk Z., Mendell J.R., Kaspar B.K. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Science Translational Medicine 2009, 1:6ra15.
20. Laval S.H., Bushby K.M. Limb-girdle muscular dystrophies-from genetics to molecular pathology. Neuropathology and Applied Neurobiology 2004, 30:91-105.
21. Lee S.J. Quadrupling muscle mass in mice by targeting TGF-beta signaling pathways. PLoS One 2007, 2:e789.
22. Malik V., Rodino-Klapac L.R., Viollet L., Wall C., King W., Al-Dahhak R., Lewis S., Shilling C.J., Kota J., Serrano-Munuera C., Hayes J., Mahan J.D., Campbell K.J., Banwell B., Dasouki M., Watts V., Sivakumar K., Bien-Willner R., Flanigan K.M., Sahenk Z., Barohn R.J., Walker C.M., Mendell J.R. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Annals of Neurology 2010, 67:771-780.
23. Mann C.J., Honeyman K., Cheng A.J., Ly T., Lloyd F., Fletcher S., Morgan J.E., Partridge T.A., Wilton S.D. Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. Proceedings of the National Academy of Sciences of the United States of America 2001, 98:42-47.
24. McPherron A.C., Lawler A.M., Lee S.J. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997, 387:83-90.
25. McPherron A.C., Lee S.J. Double muscling in cattle due to mutations in the myostatin gene. Proceedings of the National Academy of Sciences of the United States of America 1997, 94:12457-12461.
26. Mendell J.R., Buzin C.H., Feng J., Yan J., Serrano C., Sangani D.S., Wall C., Prior T.W., Sommer S.S. Diagnosis of Duchenne dystrophy by enhanced detection of small mutations. Neurology 2001, 57:645-650.
27. Mendell J.R., Campbell K., Rodino-Klapac L., Sahenk Z., Shilling C., Lewis S., Bowles D., Gray S., Li C., Galloway G., Malik V., Coley B., Clark K.R., Li J., Xiao X., Samulski J., McPhee S.W., Samulski R.J., Walker C.M. Dystrophin immunity in Duchenne's muscular dystrophy. New England Journal of Medicine 2010, 363:1429-1437.
28. Mendell J.R., Moxley R.T., Griggs R.C., Brooke M.H., Fenichel G.M., Miller J.P., King W., Signore L., Pandya S., Florence J., Schierbecker J., Robison J., Kaiser K., Mandel S., Arfken C., Gilder B. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. New England Journal of Medicine 1989, 320:1592-1597.
29. Mendell J.R., Rodino-Klapac L.R., Rosales-Quintero X., Kota J., Coley B.D., Galloway G., Craenen J.M., Lewis S., Malik V., Shilling C., Byrne B.J., Conlon T., Campbell K.J., Bremer W.G., Viollet L., Walker C.M., Sahenk Z., Clark K.R. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Annals of Neurology 2009, 66:290-297.
30. Mendell J.R., Rodino-Klapac L.R., Rosales X.Q., Coley B.D., Galloway G., Lewis S., Malik V., Shilling C., Byrne B.J., Conlon T., Campbell K.J., Bremer W.G., Taylor L.E., Flanigan K.M., Gastier-Foster J.M., Astbury C., Kota J., Sahenk Z., Walker C.M., Clark K.R. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Annals of Neurology 2010, 68:629-638.
31. Mendell J.R., Shilling C., Leslie N.D., Flanigan K.M., al-Dahhak R., Gastier-Foster J., Kneile K., Dunn D.M., Duval B., Aoyagi A., Hamil C., Mahmoud M., Roush K., Bird L., Rankin C., Lilly H., Street N., Chandrasekar R., Weiss R.B. Evidence based path to newborn screening for duchenne muscular dystrophy. Annals of Neurology 2012, 71:304-313.
32. Mendell J.R., Vaughn A.J. Duchenne muscular dystrophy: ethical and emotional considerations in long-term management. Seminars in Neurology 1984, 4:98-103.
33. Moore S.A., Shilling C.J., Westra S., Wall C., Wicklund M.P., Stolle C., Brown C.A., Michele D.E., Piccolo F., Winder T.L., Stence A., Barresi R., King N., King W., Florence J., Campbell K.P., Fenichel G.M., Stedman H.H., Kissel J.T., Griggs R.C., Pandya S., Mathews K.D., Pestronk A., Serrano C., Darvish D., Mendell J.R. Limb-girdle muscular dystrophy in the United States. Journal of Neuropathology and Experimental Neurology 2006, 65:995-1003.
34. Mosher D.S., Quignon P., Bustamante C.D., Sutter N.B., Mellersh C.S., Parker H.G., Ostrander E.A. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genetics 2007, 3:e79.
35. Rabinowitz J.E., Rolling F., Li C., Conrath H., Xiao W., Xiao X., Samulski R.J. Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. Journal of Virology 2002, 76:791-801.
36. Rodino-Klapac L.R., Janssen P.M., Montgomery C.L., Coley B.D., Chicoine L.G., Clark K.R., Mendell J.R. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. Journal of translational medicine 2007, 5:45.
37. Rodino-Klapac L.R., Montgomery C.L., Bremer W.G., Shontz K.M., Malik V., Davis N., Sprinkle S., Campbell K.J., Sahenk Z., Clark K.R., Walker C.M., Mendell J.R., Chicoine L.G. Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Molecular Therapy 2010, 18:109-117.
38. Rodino-Klapac L.R., Montgomery C.L., Mendell J.R., Chicoine L.G. AAV-mediated gene therapy to the isolated limb in rhesus macaques. Methods in Molecular Biology 2011, 709:287-298.
39. Schuelke M., Wagner K.R., Stolz L.E., Hubner C., Riebel T., Komen W., Braun T., Tobin J.F., Lee S.J. Myostatin mutation associated with gross muscle hypertrophy in a child. New England Journal of Medicine 2004, 350:2682-2688.
40. Shield M.A., Haugen H.S., Clegg C.H., Hauschka S.D. E-box sites and a proximal regulatory region of the muscle creatine kinase gene differentially regulate expression in diverse skeletal muscles and cardiac muscle of transgenic mice. Molecular and Cellular Biology 1996, 16:5058-5068.
41. van Deutekom J.C., Janson A.A., Ginjaar I.B., Frankhuizen W.S., Aartsma-Rus A., Bremmer-Bout M., den Dunnen J.T., Koop K., van der Kooi A.J., Goemans N.M., de Kimpe S.J., Ekhart P.F., Venneker E.H., Platenburg G.J., Verschuuren J.J., van Ommen G.J. Local dystrophin restoration with antisense oligonucleotide PRO051. New England Journal of Medicine 2007, 357:2677-2686.
42. Wagner K.R., Fleckenstein J.L., Amato A.A., Barohn R.J., Bushby K., Escolar D.M., Flanigan K.M., Pestronk A., Tawil R., Wolfe G.I., Eagle M., Florence J.M., King W.M., Pandya S., Straub V., Juneau P., Meyers K., Csimma C., Araujo T., Allen R., Parsons S.A., Wozney J.M., Lavallie E.R., Mendell J.R. A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Annals of Neurology 2008, 63:561-571.
43. Wang B., Li J., Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proceedings of the National Academy of Sciences of the United States of America 2000, 97:13714-13719.
44. Watchko J., O'Day T., Wang B., Zhou L., Tang Y., Li J., Xiao X. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Human Gene Therapy 2002, 13:1451-1460.
45. Welch E.M., Barton E.R., Zhuo J., Tomizawa Y., Friesen W.J., Trifillis P., Paushkin S., Patel M., Trotta C.R., Hwang S., Wilde R.G., Karp G., Takasugi J., Chen G., Jones S., Ren H., Moon Y.C., Corson D., Turpoff A.A., Campbell J.A., Conn M.M., Khan A., Almstead N.G., Hedrick J., Mollin A., Risher N., Weetall M., Yeh S., Branstrom A.A., Colacino J.M., Babiak J., Ju W.D., Hirawat S., Northcutt V.J., Miller L.L., Spatrick P., He F., Kawana M., Feng H., Jacobson A., Peltz S.W., Sweeney H.L. PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007, 447:87-91.
46. Yazaki M., Yoshida K., Nakamura A., Koyama J., Nanba T., Ohori N., Ikeda S. Clinical characteristics of aged Becker muscular dystrophy patients with onset after 30 years. European Neurology 1999, 42:145-149.
47. Yokota T., Lu Q.L., Partridge T., Kobayashi M., Nakamura A., Takeda S., Hoffman E. Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Annals of Neurology 2009, 65:667-676.
48. Zebracki K., Drotar D. Pain and activity limitations in children with Duchenne or Becker muscular dystrophy. Developmental Medicine and Child Neurology 2008, 50:546-552.