Management Of Duchenne Muscular Dystrophy Research Articles

Effectiveness of low-intensity aerobic exercise with assisted bicycle exercises on quality of life and lung functions in du-chenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by abnormalities in the dystrophin gene that affects one in every 3,500 males. In India, approximately 0.8 million were involved. Management is usually multidirectional and more focused on improving the quality of life (QOL), not mortality. Physiotherapy and exercise are an integral part of the management of DMD. Since there were no recommended exercises for DMD, there is a need to create an exercise protocol that improves the QOL. Low-intensity aerobic exercises are highly recommended for older people and are found effective. Objective: The study aimed to identify the effectiveness of low-intensity aerobic exercise with assisted bicycle exercises on QOL and lung functions in DMD. Methods: A randomized controlled trial was conducted at the Institute of Muscular Dystrophy and Research Centre, Jeevan Foundation, Veeravanalur, Tirunelveli Dist. Tamil Nadu, India. The institute has around 200 children with DMD. This study selected 34 children based on the criteria. I, the children, were provided with low-intensity aerobic exercise for seventeen children. Group II provided the children with assisted bicycle exercises for seventeen children. Both groups received exercises for 60 minutes and deep diaphragmatic breathing for 10 minutes. All are given a home program to the children. The total study duration is ten weeks. Results: Data were analysed following the assessment of Quality of life using DMD QoL and the Lung function using a spirometer (FVC, FEV1, FEV1/VC). All the data were collected on day 1, every two months. Parametric tests were used to compare the outcome measures. The student t value for the DMD QOL is 9.66 with p <0.001, the spirometry values of FEV1 are 7.67 with p< 0.001, and FVC is 14.78 with p < 0.001, respectively, and FEV1/VC is 10.81 with p < 0.001. Conclusion: This study concluded that low-intensity aerobic exercises and assisted bicycle training improve the QOL and lung functions. On comparing the interventions, it was found that low-intensity aerobic exercises are better improved than the assisted bicycle group.

Clinical practice guidelines for the diagnosis and management of Duchenne muscular dystrophy: a scoping review.

Our objective was to identify recent CPGs for the diagnosis and management of DMD and summarize their characteristics and reliability. We conducted a scoping review of CPGs using MEDLINE, the Turning Research Into Practice (TRIP) database, Google Scholar, guidelines created by organizations, and other repositories to identify CPGs published in the last 5 years. Our protocol was drafted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses for scoping reviews. To assess the reliability of the CPGs, we used all the domains included in the Appraisal of Guidelines Research and Evaluation II. We selected three CPGs published or updated between 2015 and 2020. All the guidelines showed good or adequate methodological rigor but presented pitfalls in stakeholder involvement and applicability domains. Recommendations were coherent across CPGs on steroid treatment, except for minor differences in dosing regimens. However, the recommendations were different for new drugs. There is a need for current and reliable CPGs that develop broad topics on the management of DMD and consider the challenges of developing recommendations for RDs.

Role of Siddha in Management of Duchenne Muscular Dystrophy to Reinforce the Quality of Life - A Pediatric Case Report

Role of Siddha in Management of Duchenne Muscular Dystrophy to Reinforce the Quality of Life - A Pediatric Case Report

Approaches and Directions for the Physiotherapeutic Management of Patients with “Duchenne” Muscular Dystrophy

Duchenne muscular dystrophy (DMD) affects cardiac and skeletal muscles but represents a condition that causes numerous secondary pathologies. Although there is no curative treatment available, multidisciplinary approaches, centered on the needs of the patient, improve the quality and duration of life. Therapies such as physiotherapy, occupational therapy, physical activities, and respiratory physiotherapy, but also the management of cardiac, osteo-muscular, and neuro-psychiatric manifestations, are continuously developing, (as new data becomes available) and are the key to DMD management today. These multidisciplinary approaches can lead to good long-term outcomes by helping patients with muscular dystrophy reduce muscle damage, early detect and treat heart failure, and manage cognitive impairment as best they can.

Resolution of fibrosis in mdx dystrophic mouse after oral consumption of N-163 strain of Aureobasidium pullulans produced β-glucan

Recent advances in the management of Duchenne muscular dystrophy (DMD), such as exon skipping and gene therapy, though have reached a clinical stage, the outcome at its best is still considered suboptimal. In this study, we evaluated a novel N-163 strain of Aureobasidium pullulans produced β-glucan (Neu-REFIX) for its potential as an adjuvant to slow down the progression of the disease by anti-inflammatory and anti-fibrotic effects. In this study, 45 mice in the three groups, 15 each in a group; Gr. 1 normal mice, Gr.2 mdx mice as vehicle, and Gr.3 mdx mice administered the N-163 β-glucan for 45 days. The N-163 β-glucan group showed a significant decrease in the plasma ALT, AST, and LDH levels (126 ± 69 U/l, 634 ± 371 U/l, 3335 ± 1258 U/l) compared with the vehicle group (177 ± 27 U/l, 912 ± 126 U/l, 4186 ± 398 U/l). Plasma TGF-β levels increased, and plasma IL-13 levels decreased in the N-163 group. The inflammation score of HE-stained muscle sections in the N-163 group (1.5 ± 0.8) was lower than that in the vehicle group (2.0 ± 0.8). The N-163 strain β-glucan group (24.22 ± 4.80) showed a significant decrease in the fibrosis area (Masson’s Trichrome-positive area) compared with the vehicle group (36.78 ± 5.74). The percentage of centrally nucleated fibres evaluated by Masson’s trichrome staining was 0 in the normal group, while it increased to 80% in the vehicle group but remained at 76.8% in the N-163 group. The N-163 β-glucan group showed a significant decrease in the fibrosis area. Considering their safety and easy oral consumption, Neu-REFIX β-glucan could be worth large multicentre clinical studies as adjuvant in slowing down the progress of DMD.

The Adiponectin Receptor Agonist, ALY688: A Promising Therapeutic for Fibrosis in the Dystrophic Muscle.

Duchenne muscular dystrophy (DMD) is one of the most devastating myopathies, where severe inflammation exacerbates disease progression. Previously, we demonstrated that adiponectin (ApN), a hormone with powerful pleiotropic effects, can efficiently improve the dystrophic phenotype. However, its practical therapeutic application is limited. In this study, we investigated ALY688, a small peptide ApN receptor agonist, as a potential novel treatment for DMD. Four-week-old mdx mice were subcutaneously treated for two months with ALY688 and then compared to untreated mdx and wild-type mice. In vivo and ex vivo tests were performed to assess muscle function and pathophysiology. Additionally, in vitro tests were conducted on human DMD myotubes. Our results showed that ALY688 significantly improved the physical performance of mice and exerted potent anti-inflammatory, anti-oxidative and anti-fibrotic actions on the dystrophic muscle. Additionally, ALY688 hampered myonecrosis, partly mediated by necroptosis, and enhanced the myogenic program. Some of these effects were also recapitulated in human DMD myotubes. ALY688's protective and beneficial properties were mainly mediated by the AMPK-PGC-1α axis, which led to suppression of NF-κβ and TGF-β. Our results demonstrate that an ApN mimic may be a promising and effective therapeutic prospect for a better management of DMD.

Duchenne Muscular Dystrophy Management and Treatment Access Challenges: Case Report

Introduction: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease that causes muscle weakness with respiratory and cardiac complications. International DMD standard of care guidelines exist, but their implementation and DMD treatment access in the Middle East have historically been challenging. This report highlights sub-optimal management of DMD in the Middle East together with recommendations for best practices, and the first reported use of ataluren, a mutation-specific treatment for nonsense mutation DMD (nmDMD), in this region. Case Presentation: The management of two patients in the United Arab Emirates diagnosed with nonsense mutation DMD is described. Under multidisciplinary care, both patients were treated with corticosteroids as per international DMD standard of care guidelines. Although both patients presented with typical DMD signs/symptoms, one received a genetic diagnosis and treatment relatively late owing to low awareness of the early signs and symptoms of DMD among physicians in the region; delayed genetic diagnosis of DMD hinders early initiation of mutation-specific treatments such as ataluren. Moreover, this patient demonstrated low adherence to the treatment plan, potentially resulting from low DMD awareness and poor understanding of the-risk-benefit of corticosteroids in the patient’s family. In contrast, the other patient was genetically diagnosed early at 25 months, was administered ataluren whilst ambulatory, and demonstrated high adherence to the management plan. Limited expertise in performing motor function assessments and complications with medical insurance for ataluren in the region created additional obstacles in the management of both patients. Conclusions: The contrasting experiences of these patients highlight the high variability of diagnosis and management of DMD in the Middle East. There is a need in the region to boost disease education for both public and professional communities, establish local DMD networks and guidelines, and improve access to treatments to improve the quality of care that patients with DMD receive.

Vascular therapy for Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the wasting of the muscles that eventually lead to difficulty moving and, ultimately, premature death from heart and respiratory complications. DMD deficiency is caused by mutations in the gene encoding dystrophin, which prevents skeletal muscle, cardiac muscle, and other cells from producing the functional protein. Located on the cytoplasmic face of the plasma membrane of muscle fibers, dystrophin serves as a component of the dystrophin glycoprotein complex (DGC), mechanically reinforces the sarcolemma, and stabilizes the DGC, preventing it from contraction-mediated muscle degradation. In DMD muscle, dystrophin deficiency leads to progressive fibrosis, myofiber damage, chronic inflammation, and dysfunction of the mitochondria and muscle stem cells. Currently, DMD is incurable, and treatment involves the administration of glucocorticoids in order to delay disease progression. In the presence of developmental delay, proximal weakness, and elevated serum creatine kinase levels, a definitive diagnosis can usually be made after an extensive review of the patient's history and physical examination, as well as confirmation through muscle biopsy or genetic testing. Current standards of care include the use of corticosteroids to prolong ambulation and delay the onset of secondary complications, including respiratory muscle and cardiac functions. However, different studies have been carried out to show the relationship between vascular density and impaired angiogenesis in the pathogenesis of DMD. Several recent studies on DMD management are vascular targeted and focused on ischemia as a culprit for the pathogenesis of DMD. This review critically discusses approaches-such as modulation of nitric oxide (NO) or vascular endothelial growth factor (VEGF)-related pathways-to attenuate the dystrophic phenotype and enhance angiogenesis.

Inhibiting the inflammasome with MCC950 counteracts muscle pyroptosis and improves Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common inherited human myopathy. Typically, the secondary process involving severe inflammation and necrosis exacerbate disease progression. Previously, we reported that the NLRP3 inflammasome complex plays a crucial role in this disorder. Moreover, pyroptosis, a form of programmed necrotic cell death, is triggered by NLRP3 via gasdermin D (GSDMD). So far, pyroptosis has never been described either in healthy muscle or in dystrophic muscle. The aim of this study was to unravel the role of NLRP3 inflammasome in DMD and explore a potentially promising treatment with MCC950 that selectively inhibits NLRP3. Four-week-old mdx mice (n=6 per group) were orally treated for 2 months with MCC950 (mdx-T), a highly potent, specific, small-molecule inhibitor of NLRP3, and compared with untreated (mdx) and wild-type (WT) mice. In vivo functional tests were carried out to measure the global force and endurance of mice. Ex vivo biochemical and molecular analyses were performed to evaluate the pathophysiology of the skeletal muscle. Finally, in vitro tests were conducted on primary cultures of DMD human myotubes. After MCC950 treatment, mdx mice exhibited a significant reduction of inflammation, macrophage infiltration and oxidative stress (-20 to -65%, P<0.05 vs untreated mdx). Mdx-T mice displayed considerably less myonecrosis (-54%, P<0.05 vs mdx) and fibrosis (-75%, P<0.01 vs mdx). Moreover, a more mature myofibre phenotype, characterized by larger-sized fibres and higher expression of mature myosin heavy chains 1 and 7 was observed. Mdx-T also exhibited enhanced force and resistance to fatigue (+20 to 60%, P<0.05 or less). These beneficial effects resulted from MCC950 inhibition of both active caspase-1 (-46%, P=0.075) and cleaved gasdermin D (N-GSDMD) (-42% in medium-sized-fibres, P<0.001). Finally, the anti-inflammatory action and the anti-pyroptotic effect of MCC950 were also recapitulated in DMD human myotubes. Specific inhibition of the NLRP3 inflammasome can significantly attenuate the dystrophic phenotype. A novel finding of this study is the overactivation of GSDMD, which is hampered by MCC950. This ultimately leads to less inflammation and pyroptosis and to a better muscle maturation and function. Targeting NLRP3 might lead to an effective therapeutic approach for a better management of DMD.

A longitudinal study of creatine kinase and creatinine levels in Duchenne muscular dystrophy.

Management of Duchenne muscular dystrophy (DMD) has entered an era featuring novel treatments. Trackable noninvasive biomarkers could improve disease progression monitoring and drug effect detection. Our aim in this study was to measure changes in selected noninvasive biomarkers and assess their relationship to age and motor function. We retrospectively studied 555 patients with DMD who had at least 12 months of treatment of glucocorticoids and were not enrolled in trials of potential disease-modifying therapies. We extracted biomarker data of serum creatine kinase (CK), serum creatinine (Cr), urine Cr, and urine Cr/urine osmolality (osm), as well as functional data for age at loss of ambulation and Functional Motor Scale (FMS) values from patients' clinical records. Data were analyzed using linear mixed-model analyses. CK, serum Cr, urine Cr, and urine Cr/urine osm all decreased with declining motor function. CK consistently decreased and FMS score consistently worsened with age without clear inflection points. There was an increased odds ratio for LOA with lower values of CK, serum Cr, urine Cr, and urine Cr/urine osm, most notably for urine Cr. Although individual biomarker values are challenging to directly apply clinically, our study has demonstrated that trends over time may complement functional measures in the assessment of individuals with DMD. Future studies could elucidate predictive utility of these biomarkers in assessing motor function changes in DMD.

Gene Therapy for Duchenne Muscular Dystrophy: Unlocking the Opportunities in Countries in the Middle East and Beyond.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder which leads to progressive muscle degeneration and weakness. Most patients die from cardiac or respiratory failure. Gene transfer therapy offers a promising approach to treating this disorder. Given the genetic disease burden, family size, and the high consanguinity rates in the Middle East, our objective is to address current practices and challenges of DMD patient care within two countries in this region, namely the United Arab Emirates and Kuwait, and to outline readiness for gene therapy. An expert panel meeting was held to discuss the DMD patient journey, disease awareness, current management of DMD, challenges faced and recommendations for improvement. Opportunities and challenges for gene therapy in both countries were also deliberated. A pre-meeting survey was conducted, and the results were used to guide the discussion during the meeting. DMD awareness is poor resulting in a delay in referral and diagnosis of patients. Awareness and education initiatives, along with an interconnected referral system could improve early diagnosis. Genetic testing is available in both countries although coverage varies. Corticosteroid therapy is the standard of care however there is often a delay in treatment initiation. Patients with DMD should be diagnosed and managed by a multi-disciplinary team in centers of excellence for neuromuscular disorders. Key success factors to support the introduction of gene therapy include education and training, timely and accessible genetic testing and resolution of reimbursement and cost issues. There are many challenges facing the management of DMD patients in the United Arab Emirates and Kuwait and most likely other countries within the Middle East. Successful introduction of gene therapy to treat DMD will require careful planning, education, capacity building and prioritization of core initiatives.

A Holistic Approach on Duchenne Muscular Dystrophy by Ayurvedic Treatment Modalities along with Traction: A Case Report

Background &amp; Objectives- Duchenne muscular dystrophy (DMD) is individual and one of the most communal and serious condition come under childhood muscular dystrophies. The incidence of DMD is 1:3500 births of males. It is an X-linked recessive disorder that occurs due to deletion or alteration of dystrophin protein, which is encoded by DMD Gene on Xp21 chromosome. As per the view of Ayurveda, we can consider this disorder as chromosomal hereditary anomalies (Bheejabhagahaavyava dushti janya Adibalapravtrutta vyadhi). Main objective of this case report was reduce the complaints of patient and improve the quality of life. Method and Material- The present study is about the management of DMD as per Ayurveda perspective. An 11 years old male child, has complaints of difficulty in walking, frequent falls while walking, difficulty in sitting or squatting. On Ayurvedic management principles, the present case was managed with palliative care (Shaman) and bio-cleansing therapy (ShodhanChiktsa). Result- After treatment, there was a significant improvement in complaints with signs and symptoms. Interpretation and conclusion- Though we are unable to rule out the disposition of genes through Ayurveda treatment modalities such as internal medicines, 5 detoxification procedures (Panchakarma) procedures, traction etc. we can effectively prolong the deterioration and improve the quality of life with correction in diet and lifestyle as per Ayurveda principles.

Perspectives on the advances in the pharmacotherapeutic management of Duchenne muscular dystrophy

ABSTRACT Introduction Duchenne muscular dystrophy (DMD) is a progressive genetic disease characterized by muscular weakness with a global prevalence of 7.1 cases per 100,000 males. DMD is caused by mutations of the dystrophin gene on the X chromosome, which is responsible for dystrophin protein production. Dystrophin is a cytoskeletal protein that contributes to structural support in muscle cells. DMD mutations result in dystrophin protein deficiency, which leads to muscle damage and the associated clinical presentation. Areas covered Corticosteroids such as prednisone and deflazacort are routinely given to patients to treat inflammation, but their use is limited by the occurrence of side effects and a lack of standardized prescribing. Exon-skipping medications are emerging as treatment options for a small portion of DMD patients, even though efficacy is uncertain. Many new therapeutics are under development that target inflammation, fibrosis, and dystrophin replacement. Expert opinion Because of side effects associated with corticosteroid use, there is need for better alternatives to the standard of care. Excessive cost is a barrier to patients receiving medications that have yet to have established efficacy. Additional therapies have the potential to help patients with DMD, although most are several years away from approval for patient use.

Patient demographics and characteristics from an ambispective, observational study of patients with duchenne muscular dystrophy in Saudi Arabia.

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that is characterized by progressive muscle weakness, resulting in disability and premature death. Onset of symptoms typically occurs at 2–3 years of age, and disease progression is managed through treatment with corticosteroids. The aim of this interim analysis is to increase disease awareness and improve patient management in Saudi Arabia (SA) through the use of data from an ongoing ambispective, observational, multicenter study evaluating characteristics of patients aged 1–14 years with genetically confirmed DMD in SA. This interim analysis examined the secondary outcomes from the study–the demographics and clinical characteristics of patients included retrospectively [data recorded (enrollment visit) between January 2014 and September 2020] and prospectively between September 2020 and April 2021. The primary outcome–the list of DMD gene mutations for the study population–will be reported at a later date. There were 177 eligible patients. Mean, standard deviation (SD) age at enrollment was 7.5 (3.0) years. Median (min, max) age at diagnosis was 7.0 (1.3, 13.8) years. At enrollment, 28.9% of patients were full-time wheelchair users, 50.0% of ambulatory patients could run, and 63.9% could climb stairs. The mean (SD) ages of patients at enrollment who were unable to run and climb stairs were 8.0 (2.7) and 7.6 (3.0) years, respectively. Speech delay (19.4%) and learning difficulties (14.9%) were the most commonly reported intellectual impairments. Physical therapy (84.2%) was the most common choice for initial management of DMD. Only 40.7% of patients received corticosteroid therapy as part of their initial management plan, rising to 59.1% at enrollment. Devices were given to 28.8% of patients for initial management, most commonly ankle-foot orthoses (26.0%) and wheelchairs (6.2%). This analysis reports data from the largest study to date to capture demographics and clinical characteristics of DMD patients in SA. The interim results show a relatively late DMD diagnosis age compared with that in other countries, and a need for improved adherence to international DMD standard of care guidelines. Therefore, there is an urgent requirement for improved DMD education and awareness among healthcare professionals and the public in SA.

Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy.

Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p < 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p < 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.

Label-free 3D characterization of cardiac fibrosis in muscular dystrophy using SHG imaging of cleared tissue.

Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the gene encoding dystrophin. It leads to repeated cycles of muscle fiber necrosis and regeneration and progressive replacement of fibers by fibrotic and adipose tissue, with consequent muscle weakness and premature death. Fibrosis and, in particular, collagen accumulation are important pathological features of dystrophic muscle. A better understanding of the development of fibrosis is crucial to enable better management of DMD. Three-dimensional (3D) characterization of collagen organization by second harmonic generation (SHG) microscopy has already proven a highly informative means of studying the fibrotic network in tissue. Here, we combine for the first-time tissue clearing with SHG microscopy to characterize in depth the 3D cardiac fibrosis network from DMDmdx rat model. Heart sections (1-mm-thick) from 1-year-old wild-type (WT) and DMDmdx rats were cleared using the CUBIC protocol. SHG microscopy revealed significantly greater collagen deposition in DMDmdx versus WT sections. Analyses revealed a specific pattern of SHG+ segmented objects in DMDmdx cardiac muscle, characterized by a less elongated shape and increased density. Compared with the observed alignment of SHG+ collagen fibers in WT rats, profound fiber disorganization was observed in DMDmdx rats, in which we observed two distinct SHG+ collagen fiber profiles, which may reflect two distinct stages of the fibrotic process in DMD. The current work highlights the interest to combine multiphoton SHG microscopy and tissue clearing for 3D fibrosis network characterization in label free organ. It could be a relevant tool to characterize the fibrotic tissue remodeling in relation to the disease progression and/or to evaluate the efficacy of therapeutic strategies in preclinical studies in DMD model or others fibrosis-related cardiomyopathies diseases.

Ayurveda interventions in the management of Duchenne Muscular Dystrophy – A Review

Abstract Duchenne Muscular Dystrophy (DMD) is a heterogeneous group of inherited disorders caused due to mutation in the gene for the protein dystrophin, located on the short arm of the X chromosome in the Xp21 region. It is characterized by proximal muscle weakness, calf hypertrophy, frequently developing contractures, and loss of walking by the 2nd decade. Patients are predisposed to severe, fatal pulmonary infections and lose their lives due to dysfunction of muscles involving the respiratory system. The incidence is 1 in 5000 live boys. Objective: To review existing human case reports and clinical trials for treating Duchenne muscular dystrophy through the Panchakarma interventions. Design: The literature research comprised an electronic database from January 2000 to April 2021. The study included MEDLINE, PubMed, The Cochrane Library, Google scholar, Ayush research portal and DHARA database. Search terms were used “Duchenne muscular dystrophy”, “Ayurveda”, “Panchakarma”, “DMD” No limits were used. The search strategy was adapted for each database as necessary. Only trials on humans were included in the patient review. The study applied inclusion criteria while screening the records. Intervention: Treatment with any regimen of “Panchakarma”. Outcome measures: Number and results of studies identified in the review. Results: Seventeen articles were screened; Eight human trials met inclusion criteria. Ayurvedic Panchakarma based procedures effectively relieve the signs and symptoms and reduce the CPK level in children with DMD. There are only few studies published in Ayurveda in the management of DMD. The Conventional System of medicine and Ayurveda System of medicine are at the same level in the case of DMD for therapeutic purposes as there is no permanent cure for this disease in both systems. A combined approach should be made to manage this disease with the conventional method of medicine and Ayurveda. The integrative approach could open new hope for patients of DMD, and it is a need of time.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disordercharacterised by progressivemuscle weakness beginning in early childhood.Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis,pneumonia, or the need for ventilatory support.There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weaknessin general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase,and two trialsregistersto 23 March2021,together with reference checking, citation searching, and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria.We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane.We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC andhospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function,forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenoneon respiratory function compared to placebo. The trial that contributed numerical data includedpatientswith a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion,with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome,idebenonemay resultin less of a decline from baseline inFEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) andPEF(MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenonewas associated with fewer serious adverse events(RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) andlittle to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo.Idebenonemay result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexorsand MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacyanalysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenonemay result in slightly less of a decline in FVCandless of a decline inFEV1andPEF, but probably has little to no measurable effect on change in quality of life. Idebenoneis associated with fewer serious adverse events than placebo. Idebenonemay result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data.Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disordercharacterised by progressivemuscle weakness beginning in early childhood.Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis,pneumonia, or the need for ventilatory support.There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weaknessin general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase,and two trialsregistersto 23 March2021,together with reference checking, citation searching, and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria.We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane.We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC andhospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function,forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenoneon respiratory function compared to placebo. The trial that contributed numerical data includedpatientswith a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion,with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome,idebenonemay resultin less of a decline from baseline inFEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) andPEF(MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenonewas associated with fewer serious adverse events(RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) andlittle to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo.Idebenonemay result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexorsand MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacyanalysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenonemay result in slightly less of a decline in FVCandless of a decline inFEV1andPEF, but probably has little to no measurable effect on change in quality of life. Idebenoneis associated with fewer serious adverse events than placebo. Idebenonemay result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data.Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences?

Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.