by Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. It is caused by the absence of dystrophin, a protein that helps keep muscle cells intact. DMD affects approximately 1 in 5,000 newborn boys worldwide, making it the most common type of muscular dystrophy.
Signs and Symptoms of DMD
The first noticeable sign of Duchenne Muscular Dystrophy Treatmentis delayed motor development or clumsiness in infants and toddlers. As the disease progresses, individuals experience progressive muscular weakness which typically leads to the inability to walk between ages 7 to 13. Without treatment, children with DMD also experience ventricular dysfunction, which can eventually lead to heart failure later in life. Progressive muscle wasting also affects the skeletal, diaphragm, and heart muscles. Other symptoms include joint contractures, scoliosis, and respiratory dysfunction.
Current Duchenne Muscular Dystrophy Treatment Options
While there is currently no cure for DMD, treatments aim to manage symptoms and improve quality of life. Corticosteroids such as deflazacort and prednisone are the current standard of care as they have been shown to help preserve muscle function and delay the loss of ambulation by around 2 years. Physiotherapy is also important to maintain muscle strength and flexibility. As respiratory issues develop, nocturnal ventilation may be necessary. Surgeries such as tendon lengthening or spinal corrective measures help with contractures and scoliosis. Recently, experimental gene therapies are showing promise as well.
Emerging Gene Therapies for DMD
Gene therapy aims to treat the underlying genetic cause of DMD by delivering functional copies of the missing dystrophin gene to muscle cells. Several promising gene therapy candidates have shown efficacy in clinical trials and are one step closer to receiving FDA approval:
– SRP-9001 (Nusinersen): The first-generation antisense oligonucleotide developed by Ionis Pharmaceuticals/Biogen binds to exon 51 on the pre-mRNA to induce skipping of this exon during RNA splicing, allowing a partially functional dystrophin protein to be produced. SRP-9001 was approved in 2016 in the US and EU for spinal muscular atrophy. Ongoing trials are evaluating its efficacy in DMD patients.
– Vyondys 53 (Golodirsen): Developed by Sarepta Therapeutics, this second-generation antisense oligonucleotide induces skipping of exon 53 during pre-mRNA splicing with the goal of producing dystrophin. In a phase III trial, Golodirsen significantly increased dystrophin levels from baseline in DMD patients aged 7-16. The FDA approved Vyondys 53 in 2019 for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.
– Lumasiran (Oxkjuven): An investigational RNAi therapy developed by Alnylam Pharmaceuticals, Lumasiran works by silencing production of hydroxyacid oxidase 1 (HAO1) to reduce toxins that build up and damage muscles in DMD. In a phase III trial, Lumasiran met its primary endpoint of reducing urinary levels of HAO1 enzyme and was well-tolerated. Alnylam submitted a new drug application to the FDA in late 2020.
– SRP-9001 (Casimersen): Similar to Golodirsen but targets exon 53, Casimersen is in late-stage development by Sarepta Therapeutics. Phase III trials showed significant increases in dystrophin production from baseline. Sarepta aims to submit a BLA for Casimersen in 2022 pending successful trial results.
Stem Cell and CRISPR Therapies
Other novel approaches are also in early-stage clinical testing for DMD. These include stem cell therapies using mesenchymal stem cells or hematopoietic stem cells to help regenerate muscle fibers. CRISPR/Cas9 gene editing shows promise as well, by permanently correcting mutations directly at the DNA level in both contracting and non-contracting muscles. Challenges still remain around delivery methods and off-target editing risks. The first CRISPR clinical trial for DMD initiated in 2021. More research is still needed but these emerging therapies represent hope that one day DMD may be reversible through genetic or cellular interventions.
Access and Cost of Emerging Treatments
As gene therapies for DMD make progress, an important next step is ensuring all patients have access to these highly promising new treatments. The current list prices are prohibitively expensive for most families and insurance plans, costing over $1 million per patient. However, conversations are ongoing between biotech companies, patient advocacy groups, and policymakers regarding value-based payment models, international partnerships, and expanded insurance coverage support to make these therapies affordable. Treatments cannot fulfill their potential to extend and improve lives if cost remains a barrier. Collaborative efforts will be crucial to tackle this challenge.
Over the past few years, research into duchenne muscular dystrophy treatment has made incredible strides. Experimental gene therapies are demonstrating the ability to produce clinically meaningful levels of the missing dystrophin protein. If successfully developed and approved, these targeted genetic strategies have the potential to transform DMD from a fatal childhood disease to one with a much milder prognosis. As therapies advance, ensuring universal access will be equally important. With ongoing clinical progress and partnerships across industry, advocates, and policy, the goal of a treatment or cure for all may become reality in the near future.
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1. Source: Coherent Market Insights, Public Source, Desk Research
2. We have leveraged AI tools to mine information and compile it.
