While gene therapy techniques continue to develop and show promise for successful application in humans, emphasis is equally being put on early intervention.
Scientists at Nationwide Children’s in collaboration with Cincinnati Children’s, the Ohio Department of Health and Centers for Disease Control and Prevention, are facilitating newborn screening for DMD at 33 Ohio hospitals to help influence early diagnosis of the condition. “Early diagnosis allows for earlier treatment, may allow families to better prepare themselves for the emotional and financial issues caused by a diagnosis of DMD, and could help families plan for future pregnancies,” said Dr. Mendell.
Dr. Mendell says early detection of comorbidities is equally as important. Muscle Group members recently identified gene mutations that may predispose patients with Becker muscular dystrophy to early onset heart conditions. The group is now funded to examine mechanisms of heart disease in Duchenne muscular dystrophy.
Genetic studies are helping to classify which type of dystrophin gene mutation patients have in order to better inform the treatments that might work for them. “As genetic screening becomes more widely available, clinicians will now be able to use this information to deliver more personalized care to patients with neuromuscular diseases,” said Dr. Mendell.
In these ways Muscle Group members continue to take critical steps toward helping patients deal with neuromuscular diseases.
Rodino-Klapac LR, Montgomery CL, Bremer WG, Shontz KM, Malik V, Davis N, Sprinkle S, Campbell KJ, Sahenk Z, Clark KR, Walker CM, Mendell JR, Chicoine LG.Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Mol Ther. 2010 Jan;18(1):109-17.
Xu R, DeVries S, Camboni M, Martin PT. Overexpression of Galgt2 reduces dystrophic pathology in the skeletal muscles of alpha sarcoglycan-deficient mice. Am J Pathol. 2009 Jul;175(1):235-47.
Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4.
Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell JR, Kaspar BK. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med. 2009 Nov 11;1(6):6ra15.
Dahlman JM, Bakkar N, He W, Guttridge DC. NF-kappaB functions in stromal fibroblasts to regulate early postnatal muscle development. J Biol Chem. 2010 Feb 19;285(8):5479-87.
Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK.Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65.
Kaspar RW, Allen HD, Ray WC, Alvarez CE, Kissel JT, Pestronk A, Weiss RB, Flanigan KM, Mendell JR, Montanaro F.Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in becker muscular dystrophy. Circ Cardiovasc Genet. 2009 Dec;2(6):544-51.
Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. LGMD2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol 2009;66:290-297