Chady H. Hakim

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The ultimate goal of muscular dystrophy gene therapy is to treat all muscles in the body. Global gene delivery was demonstrated in dystrophic mice more than a decade ago using adeno-associated virus (AAV). However, translation to affected large mammals has been challenging. The only reported attempt was performed in newborn Duchenne muscular dystrophy (DMD)(More)
Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the(More)
Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years,(More)
Loss of muscle force is a salient feature of Duchenne muscular dystrophy (DMD), a fatal disease caused by dystrophin deficiency. Assessment of force production from a single intact muscle has been considered as the gold standard for studying physiological consequences in murine models of DMD. Unfortunately, equivalent assays have not been established in(More)
The dystrophin-deficient dog is excellent large animal model for testing novel therapeutic modalities for Duchenne muscular dystrophy (DMD). Despite well-documented descriptions of dystrophic symptoms in these dogs, very few quantitative studies have been performed. Here, we developed a comprehensive set of non-invasive assays to quantify dog gait (stride(More)
The muscular dystrophies are a group of devastating genetic disorders that affect both skeletal and cardiac muscle. An effective gene therapy for these diseases requires bodywide muscle delivery. Tyrosine mutant adeno-associated virus (AAV) has been considered as a class of highly potent gene transfer vectors. Here, we tested the hypothesis that systemic(More)
Body movements are mainly provided by mechanical function of skeletal muscle. Skeletal muscle is composed of numerous bundles of myofibers that are sheathed by intramuscular connective tissues. Each myofiber contains many myofibrils that run longitudinally along the length of the myofiber. Myofibrils are the contractile apparatus of muscle and they are(More)
Oxidative stress is thought to compromise muscle contractility. However, administration of generic antioxidants has failed to convincingly improve performance during exhaustive exercise. One possible explanation may relate to the inability of the supplemented antioxidants to effectively eliminate excessive free radicals at the site of generation. Here, we(More)
The mdx mouse is the most frequently used animal model for Duchenne muscular dystrophy (DMD), a fatal muscle disease caused by the loss of dystrophin. Mdx mice are naturally occurring dystrophin-null mice on the C57BL/10 (BL10) background. We crossed black mdx to the white FVB background and generated mdx/FVB mice. Compared to that of age- and sex-matched(More)
Recent progress suggests gene therapy may one day be an option for treating some forms of limb girdle muscular dystrophy (LGMD). Nevertheless, approaches targeting LGMD have so far focused on gene replacement strategies for recessive forms of the disease. In contrast, no attempts have been made to develop molecular therapies for any of the eight dominantly(More)