Corticosteroid Treatment Impact on Spinal Deformity in Duchenne Muscular Dystrophy

Sanzarello, Ilaria; Merlini, Luciano; Traina, Francesco; Rosa, Michele Attilio; Faldini, Cesare

doi:10.1155/2014/965235

Cited by 4 publications

(4 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Progressive scoliosis develops in the majority of DMD patients as a combined result of wheelchair dependence, paralysis of the extensor muscles, contractures and growth spurts [29]. Physical therapy and the use of splints/orthoses can be useful in some patients and surgical intervention may be required for lower-limb contractures.…”

Section: Discussionmentioning

confidence: 99%

Current Management of Duchenne Muscular Dystrophy in the Middle East: Expert Report

Jumah

Muhaizea

Rumayyan

et al. 2019

Neurodegener. Dis. Manag.

View full text Add to dashboard Cite

Aim: Duchenne muscular dystrophy (DMD) is a severe and rare X-linked neuromuscular childhood disorder that results in functional decline, loss of ambulation and early death due to cardiac or respiratory failure. The objective of this paper is to address different aspects of the current management of DMD in the Middle East, north Africa (MENA) region, and to gather experts’ recommendations on how to optimally diagnose and treat patients suffering from this disease. Methods: A group of experts (neuromuscular medicine, neuropediatricians and geneticists) convened to discuss the diagnosis and management of DMD in the MENA region. A list of practical statements was prepared by the chair of the meeting to guide the discussions around critical aspects relating to the current and future management of DMD. Results & conclusion: Ideally, DMD management should be a multidisciplinary approach. Nevertheless, few tertiary care hospitals in the region are currently able to provide the full spectrum of medical expertise and services needed by DMD patients. Clinical practice in the region remains heterogeneous. Specific guidelines for diagnosis and treatment are needed in the MENA region to improve outcomes. Disease awareness among the general public and the medical community is lacking. Now that mutation-specific therapies are being developed and more widely studied, general education programs regarding early signs and symptoms, a standardized referral and diagnosis pathway, patient registries and support groups will significantly improve the management of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Current Management of Duchenne Muscular Dystrophy in the Middle East: Expert Report

Jumah

Muhaizea

Rumayyan

et al. 2019

Neurodegener. Dis. Manag.

View full text Add to dashboard Cite

show abstract

“…In summary it is now widely recognized that long-term corticosteroid therapy (1) prolongs ambulation, (2) reduces the need for spinal surgery, (3) reduces cardiopulmonary dysfunction, (4) delays the need for mechanical ventilation, and (5) increases survival and quality of life of DMD patients [ 20 , 31 , 35 , 41 , 42 , 44 ]. Recent findings also indicate that early use of corticosteroids is associated with significant advantages over delaying its use [ 20 , 28 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Improving clinical trial design for Duchenne muscular dystrophy

Merlini

Sabatelli

2015

BMC Neurol

Self Cite

View full text Add to dashboard Cite

BackgroundCurrently, the most promising therapies for Duchenne muscular dystrophy (DMD) are exon skipping and stop codon read-through, two strategies aimed at restoring the expression of dystrophin. A phase 3 clinical trial with drisapersen, a drug designed to induce exon 51-skipping, has failed to show significant improvement of the primary outcome measure, the six-minute walk test.DiscussionHere, we review some key points that should be considered when designing clinical trials for these new therapies. First, younger patients have more functional abilities and more muscle fibers to preserve than older patients and therefore are better subjects for trials designed to demonstrate the success of new treatments. Second, the inclusion of patients on corticosteroids both in the treatment and placebo groups is of concern because the positive effect of corticosteroids might mask the effect of the treatment being tested. Additionally, the reasonable expectation from these therapies is the slowing of disease progression rather than improvement. Therefore, the appropriate clinical endpoints are the prolongation of the ability to stand from the floor, climb stairs, and walk, not an increase in muscle strength or function. Hence, the time frames for the detection of new dystrophin, which occurs within months, and the ability to demonstrate a slowing of disease progression, which requires years, are strikingly different. Finally, placebo-controlled trials are difficult to manage if years of blindness are required to demonstrate a slowing of disease progression. Thus, accelerated/conditional approval for new therapies should be based on surrogate biochemical outcomes: the demonstration of de novo dystrophin production and of its beneficial effect on the functional recovery of muscle fiber.SummaryThese data suggest that clinical trials for DMD patients must be adapted to the particular characteristics of the disease in order to demonstrate the expected positive effect of new treatments.

show abstract

“…19 In DMD, corticosteroids provide various benefits including: increased muscle strength, prolonged ambulation, reduced need for scoliosis surgery and preserved respiratory and cardiac function in adults. [19][20][21][22][23][24] Corticosteroids can be used in children from 4 years of age provided they have immunity to chickenpox. These treatments, however, are associated with various risks that include weight gain, Cushingoid features, behaviour changes, growth delay, fractures, cataracts and skin changes.…”

Section: A Typical Journey In Duchenne Muscular Dystrophy -From Diagnosis To Referral Treatment and Later Developmentmentioning

confidence: 99%

Early Diagnosis and Treatment – The Use of Ataluren in the Effective Management of Duchenne Muscular Dystrophy

Quinlivan

Tuffery‐Giraud

2018

European Neurological Review

View full text Add to dashboard Cite

The understanding of the natural history of Duchenne muscular dystrophy (DMD) is increasing rapidly and new treatments are emerging that have the potential to substantially improve the prognosis for patients with this disabling and life-shortening disease. For many, however, there is a long delay between the appearance of symptoms and DMD diagnosis, which reduces the possibility of successful treatment. DMD results from mutations in the large dystrophin gene of which one-third are de novo mutations and two-thirds are inherited from a female carrier. Roughly 75% of mutations are large rearrangements and 25% are point mutations. Certain deletions and nonsense mutations can be treated whereas many other mutations cannot currently be treated. This emphasises the need for early genetic testing to identify the mutation, guide treatment and inform genetic counselling. Treatments for DMD include corticosteroids and more recently, ataluren has been approved in Europe, the first disease-modifying therapy for treating DMD caused by nonsense mutations. The use of ataluren in DMD is supported by positive results from phase IIb and phase III studies in which the treatment produced marked improvements in the 6-minute walk test, timed function tests such as the 10 m walk/run test and the 4-stair ascent/descent test compared with placebo. In these trials, ataluren was well tolerated and adverse event profiles were similar to placebo. As such disease-modifying treatments become more widely available, the outlook for children with DMD will improve but physicians must be aware of the disease, rapidly initiate testing where it is suspected and promptly begin appropriate treatment.

show abstract

Corticosteroid Treatment Impact on Spinal Deformity in Duchenne Muscular Dystrophy

Cited by 4 publications

References 82 publications

Current Management of Duchenne Muscular Dystrophy in the Middle East: Expert Report

Current Management of Duchenne Muscular Dystrophy in the Middle East: Expert Report

Improving clinical trial design for Duchenne muscular dystrophy

Early Diagnosis and Treatment – The Use of Ataluren in the Effective Management of Duchenne Muscular Dystrophy

Contact Info

Product

Resources

About