Current Status of Duchenne Muscular Dystrophy Treatment

 

Duchenne Muscular Dystrophy Treatment 

What is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to absence or defect in the protein dystrophin. DMD affects approximately 1 out of every 3,500 to 5,000 male births globally. It is caused by mutations in the DMD gene located on the X chromosome that results in the inability to produce functional dystrophin protein in muscles.

Signs and Symptoms of DMD

Many boys with DMD start showing signs and symptoms between ages 3-5 years. Common initial symptoms are calf muscle enlargement (pseudohypertrophy), difficulty climbing stairs, frequent falls, and walking on their toes. Other signs include delayed ability to stand up from lying down, difficulty with running and jumping, and general muscle weakness. As the disease progresses, the muscle weakness spreads to other parts of the body like hips, spine, shoulders, and respiratory muscles. Eventually patients may become wheelchair-bound in their teens and require ventilator support in late adolescence or early adulthood.

Current Duchenne Muscular Dystrophy Treatment

Though there is no cure for Duchenne Muscular Dystrophy Treatment yet, various medications and therapies are used to treat symptoms and slow down disease progression. Corticosteroids like deflazacort and prednisone are the standard therapy which help preserve muscle strength and function for a longer time. Physiotherapy and bracing help maintain mobility and prevent contractures. Surgery may be required to correct spinal curvature or repair hip joints. Assistive devices like wheelchairs, crutches, braces are prescribed as needed. Respiratory support through cough assist and non-invasive ventilation preserve lung function. Gene therapies and exon skipping therapies are among the most promising experimental treatments being researched.

Glucocorticoid Corticosteroid Treatment

Corticosteroids have been the mainstay treatment for DMD for last three decades. The mechanism involved is reducing inflammation that occurs inside muscles during degeneration and regeneration processes. Deflazacort and prednisone are the commonly used glucocorticoids. Clinical trials have demonstrated corticosteroids treatment prolongs standing ability and delays the need for wheelchair by around 2 years. However, long term usage also leads to side effects like weight gain, stunted growth, bone fragility, cataracts, behavioral changes etc. Doctors closely monitor patients on steroids treatment. The benefits appear to outweigh the risks though risk-benefit ratio needs individual determination.

Physical Therapy and Active Exercise

Physiotherapy plays a vital role in managing strength, endurance, range of motion, and mitigating contractures in DMD patients. Low-impact aerobic exercises like cycling and swimming are encouraged under supervision. Stretching and range-of-motion exercises help maintain flexibility. Strengthening exercises help fatigue-prone muscles. Aquatic therapy is suitable since water removes weight-bearing stresses. Low-weight high-repetition exercises do not cause further damage. Regular exercise slows disease progression and maintains motor skills and functions for daily living. Proper bracing, splints and adaptive equipment enable ambulation and wheelchair use. Physical therapy keeps muscles working for as long as possible.

Experimental Treatments: Gene and Exon Skipping Therapies

Emerging genetic therapies hold great hope for stopping or reversing DMD progression. Gene therapy aims to directly deliver functional copies of the faulty DMD gene to muscles via vectors like viruses. Exon skipping aims to manipulate pre-mRNA splicing so that specific exons carrying mutations are skipped and a truncated but functional dystrophin protein is expressed. Two exon skipping drugs eteplirsen and golodirsen are approved in some countries. Clinical trials show exon skipping therapy restores functional dystrophin and meaningful clinical benefit. Challenges include delivering therapeutic doses adequately to whole-body muscles. Other promising avenues being explored are CRISPR/Cas9 genome editing, stop codon read-through drugs, utrophin upregulation therapies etc. Success of initial trials fuels optimism though more research is still needed for generalized clinical use.

Palliative Care and Multidisciplinary Approach

In advanced stages of DMD, palliative care aims to maximize comfort and quality of life. A team of neurologists, cardiologists, pulmonologists, physical therapists, orthopedists provide coordinated multidisciplinary care. Nutritional support prevents malnutrition related complications. Non-invasive ventilation assists respiration as breathing muscles weaken. Management of orthopedic deformities like scoliosis and contractures allow independence for maximum time. Screening and early treatment of associated conditions like cardiomyopathy and obesity help prevent secondary issues. Regular monitoring for respiratory and cardiac functions guides timely interventions. A palliative approach together with preventive strategies and symptomatic relief optimizes care through all stages of DMD.

Future Prospects for Duchenne Muscular Dystrophy Treatment

With improved understanding of DMD pathogenesis, diagnosis and care have significantly advanced over past few decades. While curative options are still elusive, new technologies like exon skipping therapies and gene editing present realistic prospects for stopping or reversing disease progression. Restoring functional dystrophin levels has the potential to halt or reverse muscle damage if delivered before extensive fibrosis sets in. Combining gene and cell therapies in a staged approach may address different tissue types and disease stages. Designing personalized treatment plans based on disease severity, genotype and patient circumstances will optimize benefit-risk ratios. Industry-academia partnerships worldwide are accelerating research and clinical testing. With continued research support, it is reasonable to expect major therapeutic breakthroughs for DMD in the coming decade.

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