Emerging drugs for Duchenne muscular dystrophy

Malik, Vinod; Rodino‐Klapac, Louise R.; Mendell, Jerry R.

doi:10.1517/14728214.2012.691965

Cited by 90 publications

(63 citation statements)

References 130 publications

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“…In skeletal muscle the impact of ROS is physiologically well contained through the activation of an endogenous program of antioxidant response, including the expression of redox-sensitive transcription factors [68][69][70][71]. However, elevated levels of free radicals generated under pathologic conditions can overwhelm the antioxidant defense leading to protein carbonylation and DNA damage.…”

Section: Oxidative Stressmentioning

confidence: 99%

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Insights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin

Forcina

Pelosi

Miano

et al. 2017

JFMK

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Duchenne muscular dystrophy (DMD) is an X-linked genetic disease in which the dystrophin gene is mutated, resulting in dysfunctional dystrophin protein. Without dystrophin, the dystrophin-glycoprotein complex (DGC) is unstable, leading to an increase in muscle damage. Moreover, the imbalance between muscle damage and repair leads to a chronic inflammatory response and an increase in the amount of fibrosis over time. The absence of dystrophin at the sarcolemma also delocalizes and downregulates nitric oxide synthase (nNOS) and alters enzymatic antioxidant responses, leading to an increase in oxidative stress. In this review, we analyze the pathogenic role of both inflammation and oxidative stress in muscular dystrophy.

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Section: Oxidative Stressmentioning

confidence: 99%

“…Moreover, antioxidant drugs can be an important therapeutic option to counteract the secondary signs of dystrophinopathy [68]. Clinical studies using the synthetic derivative of coenzyme Q10, namely idebenone, revealed the efficacy of antioxidant drugs for DMD treatment.…”

Section: Therapeutic Approaches Direct Against Pathogenic Mechanisms mentioning

confidence: 99%

Insights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin

Forcina

Pelosi

Miano

et al. 2017

JFMK

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“…http://dx.doi.org/10.1101/012344 doi: bioRxiv preprint first posted online Dec. 8, 2014; In addition to corticosteroids, there are a number of therapies and clinical trials in development based on the tremendous knowledge about DMD pathophysiology [15].…”

Section: Cc-by-nd 40 International License Peer-reviewed) Is the Autmentioning

confidence: 99%

Online Self-Report Data for Duchenne Muscular Dystrophy confirms natural history and can be used to assess for therapeutic benefits

Wang

Fadlon

Ulm

et al. 2014

Preprint

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To assess the utility of online patient self-report outcomes in a rare disease, we attempted to observe the effects of corticosteroids in delaying age at fulltime wheelchair use in Duchenne muscular dystrophy (DMD) using data from 1,057 males from DuchenneConnect, an online registry. Data collected were compared to prior natural history data in regard to age at diagnosis, mutation spectrum, and age at loss of ambulation. Because registrants reported differences in steroid and other medication usage, as well as age and ambulation status, we could explore these data for correlations with age at loss of ambulation. Using multivariate analysis, current steroid usage was the most significant and largest independent predictor of improved wheelchair-free survival. Thus, these online self-report data were sufficient to retrospectively observe that current steroid use by patients with DMD is associated with a delay in loss of ambulation. Comparing commonly used steroid drugs, deflazacort prolonged ambulation longer than prednisone (median 14 years and 13 years, respectively). Further, use of Vitamin D and Coenzyme Q10, insurance status, and age at diagnosis after 4 years were also significant, but smaller, independent predictors of longer wheelchair-free survival. Nine other common supplements were also individually tested but had lower study power. This study demonstrates the utility of DuchenneConnect data to observe therapeutic differences, and highlights needs for improvement in quality and quantity of patient-report data, which may allow exploration of drug/therapeutic practice combinations impractical to study in clinical trial settings.

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“…Additional targets include the reduction of inflammation or the promotion of skeletal muscle blood flow and muscle contractility using nitric oxide (NO) donors [14].…”

Section: Discussionmentioning

confidence: 99%

Extracorporeal Shock Waves in the Treatment of Equinovarus Foot in a Duchenne Patient: A Case Report

Barazzuol¹,

Lampropoulou²,

Meneghini³

et al. 2015

J Nov Physiother Phys Rehabil

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Background: Duchenne muscular dystrophy (DMD) is characterized by a progressive muscular weakness, with loss of independent ambulation. When the disease results in the complete loss of ambulation, one of the purposes of treatment during the latest phase is to prevent or reduce complications such as foot deformities.A 20-year-old DMD patient had a complete loss of muscular strength in the inferior and superior limbs and a severe bilateral clubfoot deformity. Active movements were not possible, while passive motion was very limited in dorsiflexion and pronation, inversion and eversion, with stronger limitation on the right foot.First, the patient was treated with gentle manipulation and casting for two weeks, but no improvement in passive range of motion was detected.The treatment was then modified by adding a session of focused extracorporeal shock wave therapy for five consecutive weeks. Results:After five shock wave sessions, both limbs showed a bilateral correction of the talometatarsal angle, respectively 26° on the right and 19° on the left foot. The most relevant improvements were estimated in the passive dorsiflexion of both ankles: with a gentle manipulation, both feet could return to the anatomical position, in such a way to allow the patient to wear his own shoes. Conclusions:There is increasing evidence that nitric oxide (NO) and vascular endothelial growth factor (VEGF) dysregulation is involved in DMD progression; on the other hand, extracorporeal shock wave therapy (ESWT) induces NO and VEGF production, thus promoting angiogenesis, and has proven effective in reducing muscular hypertone. ESWT shows a potential role in the treatment of Duchenne complications such as foot deformities, as part of a multidisciplinary rehabilitation program.of their antagonist muscle tendons 6 . When ambulation is no longer possible, the rehabilitation program focuses on the prevention or reduction of complications and deformities, in order to alleviate pain and pressure, to allow the patient to wear shoes, and to correctly place the feet on wheelchair footrests [7].Despite the absence of a specific treatment, the natural history of the DMD can be in part modified [1].Since the surgical therapy showed controversial results on long term effectiveness, there has been a growing consideration on the conservative approach, including drugs and rehabilitation. Nevertheless, in most studies the rehabilitation programme includes stretching, eccentric and aerobic exercise, sub maximum strengthening activity when residual strength is higher, while few authors emphasize the role of physical energies, like whole-body vibration [8,9] and laser therapy [10].Extracorporeal shock wave therapy (ESWT) is a relatively recent method used in the treatment of many musculoskeletal disorders, such as tendinopathies and non-union fractures.Over the past few years, ESWT has received a widespread consensus in many other fields, including in the treatment of spastic hypertone in patients affected by stroke: even a single session of shock

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Emerging drugs for Duchenne muscular dystrophy

Cited by 90 publications

References 130 publications

Insights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin

Insights into the Pathogenic Secondary Symptoms Caused by the Primary Loss of Dystrophin

Online Self-Report Data for Duchenne Muscular Dystrophy confirms natural history and can be used to assess for therapeutic benefits

Extracorporeal Shock Waves in the Treatment of Equinovarus Foot in a Duchenne Patient: A Case Report

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