Duchenne Muscular Dystrophy (DMD) Disease

Explore the Advancements in Duchenne Muscular Dystrophy with DiseaseLandscape Insights (DLI)

The rare and severe neuromuscular disorder Duchenne Muscular Dystrophy has long been a focus of medical research, but it's not simply a mission motivated by compassion—it's also opening doors to new financial prospects in the healthcare industry.

One of the most severe types of inherited muscular dystrophy is Duchenne muscular dystrophy (DMD). The most prevalent type of muscular dystrophy that develops in childhood, DMD nearly entirely affects men. According to the National Organization for Rare Diseases, one in every 3,500 live male births is the birth prevalence. The typical age of onset is between 3 and 5 years old. In the United States, 250,000 people are thought to be affected by all muscular dystrophies.

It is the most prevalent genetic neuromuscular disorder and has no preference for any particular race or ethnicity. Dystrophin gene mutations cause gradual degradation of muscle fibers and weakening. This weakness starts out as trouble walking, but it gradually worsens to the point where affected people are unable to do activities of daily life and are forced to use wheelchairs. Death typically occurs in the twenties owing to respiratory muscle weakness orcardiomyopathy, and cardiac and orthopedic problems are frequent. To evade orthopedic difficulties, current treatment is directed at glucocorticoid therapy and physical therapy.

Fundamentally, Duchenne muscular dystrophy (DMD) is a hereditary condition with a known cause. It develops as a result of mutations in the X chromosome Dystrophin gene. The generation of functional dystrophin, a vital protein that supports the structural integrity of muscle cells, is hampered by these genetic abnormalities. Muscular fibers without dystrophin become brittle and more likely to be harmed during contractions, which causes the gradual muscular degeneration associated with DMD. DMD typically affects males because of its X-linked recessive inheritance pattern. Males have one X and one Y chromosome, hence DMD is caused by a mutation in the one dystrophin gene on the X chromosome. Females with two X chromosomes, however, can have the mutant dystrophin gene without exhibiting any symptoms and nonetheless pass the mutation on to their offspring. For diagnostic testing, genetic counseling for at-risk families, and the continued development of potential gene-based therapeutics targeted at targeting the underlying genetic etiology of this life-threatening disease, understanding the genetic foundation of DMD has been essential.

Although symptoms start as early as infancy or are seen later in childhood, Duchenne muscular dystrophy (DMD) symptoms most frequently manifest between the ages of 2 and 4 years. DMD results in progressive muscle weakening, therefore typical symptoms include:

• Legs and pelvis first show signs of progressive muscle weakness and atrophy (loss of muscle mass). Their neck, arms, and other body parts experience it less severely.
• Hypertrophy (growth in muscular size) of the calf muscles.
• A challenge to ascend stairs.
• Walking difficulty that worsens over time.
• Recurring falls.
• Walking with a waddle.
• Toe stomping.

According to the Muscular Dystrophy Association (MDA), the prevalence of DMD is roughly 6 per 100,000 people in Europe and North America. Males are more typically affected than females since DMD is inherited in an X-linked recessive way. One in 3600 male live-born newborns are believed to be affected. According to some studies, there are 2 DMD cases for every 10,000 people in the US. One of the most prevalent and serious congenital myopathies is DMD.

Diagnostic services, medications, genetic testing, patient support, and other areas of the healthcare industry have all been impacted by the diagnosis and treatment of DMD. The market potential is anticipated to grow further as developments and DMD research evolve, giving those suffering from this fatal disease fresh hope and an enhanced quality of life.

DiseaseLandscape Insights (DLI) Acts as a Guiding Light and Helps to Navigate the Captains in the Healthcare Industry to Reach the Shore and Explore Uncharted Territories.

Diagnostic Analysis –

In order to diagnose any type of muscular dystrophy, a doctor typically starts by gathering information about the patient and their family as well as completing a physical exam. Pseudohypertrophy, lumbar spine deviation, aberrant gait patterns, and various degrees of reduced muscle reflexes are possible diagnoses made by doctors. These observations reveal a wealth of information, including the pattern of weakness. Even before any difficult diagnostic procedures are performed, a patient's medical history and physical examination greatly contribute to the diagnosis.

The following tests are considered for diagnosis of DMD –

1. Creatine Kinase Blood Test –

In the diagnosis process, doctors recommend a blood test and check the CK levels. CK stands for Creatine Kinase – an enzyme that is expelled from damaged muscles. An elevated CK level usually means the muscle is being fragmented by some malformed or peculiar process, such as muscular dystrophy. High CK levels indicate that the muscles themselves are the cause of weakness, even though it does not indicate the type of muscle disorder that might be occurring. High levels of CK are found even in newborns affected by DMD. CK levels peak by the age of 2 and then progressively fall at a rate of ~25% per year, returning to normal levels.

2. Gene Analysis/ Genetic Testing –

Patients with DMD exhibit a completely absent or nearly nonexistent dystrophin gene. Dystrophin immunoblotting is often utilized to assess the disease's severity. Patients with DMD are discovered to have less than 5% of the amount of dystrophin that is considered normal.

Employment of Polymerase Chain Reactions (PCR) finds up to ~98% of mutations. Duplications and deletions are also found using multiplex ligation-dependent probe amplification (MPLA).  In-frame or out-of-frame transcription products result from duplications. Although less frequently utilized, Fluorescence In Situ Hybridization (FISH) is potentially helpful in locating tiny point mutations. Dystrophin immunocytochemistry is also used to find patients that PCR was unable to identify.

3. Electrocardiogram (ECG) –

Deep Q waves in leads I, aVL, and V5–6 and tall R waves in leads V1–V6 with an elevated R/S ratio are characteristic ECG alterations. Telemetry is a way to find conduction anomalies associated witharrhythmias. Supraventricular arrhythmias are more prevalent, as was already mentioned. In DMD, aberrant intra-atrial conduction is more frequent than AV or infra-nodal anomalies.

4. Muscle Biopsy –

Muscle fiber necrosis with a mononuclear cell infiltrate, dispersed degeneration, regeneration of myofibers, and replacement of muscle with adipose tissue and fat are all visible during a muscle biopsy. The gastrocnemius and quadriceps femoris were the muscles that underwent biopsy.

Treatment Analysis –

Duchenne muscular dystrophy (DMD) currently has no known cure, but the search for efficient treatments and disease-modifying medications has sparked a booming market for creative healthcare solutions. Due to this unmet medical need, significant funds have been invested in research, clinical trials, and the creation of novel medicines, ranging from exon-skipping medications to gene-editing technology. The demand for novel treatments is generating market opportunities in pharmaceuticals, genetic diagnostics, therapeutic equipment, and specialized patient support services as the world's attention to DMD increases. This is going to contribute to greater care and the promise of a better future for people and families affected by this devastating disease.

The currently available muscular dystrophy treatment options are –

1. Medications –

• Corticosteroids - Prednisolone and Deflazacort are examples of corticosteroids that are helpful for preventing Muscular Atrophy, enhancing lung function, postponing scoliosis, reducing the onset of cardiomyopathy (heart weakness), and extending survival. The FDA approved Golodirsen (Vyondys 53) in 2019 for the treatment of certain Duchenne dystrophy patients who have a specific genetic mutation.
• Medications to treat Cardiomyopathy - Early management of cardiomyopathy with ACE inhibitors and/or beta-blockers delay the onset of heart failure and slow the course of cardiomyopathy.

People with muscular dystrophy benefit from a variety of therapies and assistive technologies that enhance their quality of life and occasionally even lengthen it.

• Glucocorticoid Therapy –

Myotube apoptosis is slowed down by glucocorticoid medication, which also slows down myofiber necrosis. Patients four years of age and older who have deteriorating or plateauing muscular function are prescribed prednisone. It is advised to administer prednisone at a dosage of 0.75 mg/kg per day, or 10 mg/kg per week over two weekends.

Prednisone's oxazoline derivative Deflazacort, which has an estimated dosage equivalency of 1:1.3 when compared to prednisone and a superior adverse effect profile, is occasionally favored over prednisone. The dosage is 0.9 mg/kg/day, which is advised. According to studies, glucocorticoid therapy improves overall mortality, delays the onset of scoliosis, and slows the advancement of cardiomyopathy. It also improves pulmonary function.

Emerging Therapies in Development –

Elevidys, (delandistrogene moxeparvovec-rokl) the first gene treatment for DMD, was approved by the U.S. Food and Drug Administration (FDA) for DMD on June 22, 2023, for patients between the ages of 4 and 5. The dystrophin gene, which is mutated in DMD patients, is delivered as part of this recently approved gene therapy in a truncated, functional version. Without dystrophin, muscles degenerate because it acts as a sort of shock absorber for them. This gene therapy's shorter microdystrophin promotes better muscle health and reduces muscular atrophy.

One of the clinical trial locations for Elevidys, a drug manufactured by Sarepta Therapeutics, was the Children's Hospital of Philadelphia (CHOP). With this approval, CHOP patients will now have access to a seventh type of cell and gene therapy. Gene therapy necessitates multidisciplinary knowledge and meticulous monitoring. Since the FDA approved the first gene therapy in the United States in 2017, CHOP's medical professionals have been perfecting gene therapies. More clinical trials involving gene therapy are expected to be conducted at CHOP in the near future.

Elevidys has received FDA approval for the treatment of ambulatory pediatric Duchenne muscular dystrophy (DMD) kids aged 4 to 5 years who have a known mutation in the DMD gene. There isn't currently a test for the detection of total antibodies to AAVrh74 that has been approved by the FDA. Patients with any exon 8 or exon 9 deletions in the DMD gene should not use elevidys. Before beginning the corticosteroid regimen necessary for Elevidys infusion, patients' immunizations should be current with regard to immunization recommendations. At least 4 weeks should pass after the last vaccination before beginning the corticosteroid regimen.

Clinical Trial Assessment -

DiseaseLandscape Insights aids in clinical assessment as a mediator for successful outcomes as well as a navigator in the treatment, diagnostics, and evolving practices.

The below table specifies the ongoing clinical trials, their official study titles, and the phases in which they are being conducted.

Conclusion –

DiseaseLandscape Insights (DLI) is dedicated to being your reliable partner in the healthcare sector as a consultancy. Our goal is to offer complete, data-driven solutions that enable stakeholders, organizations, and healthcare professionals to make wise choices, foster innovation, and ultimately improve patient care.

We work to close the gap between difficult healthcare problems and practical solutions using our knowledge and resources. We provide the strategic direction you need to successfully navigate the ever-changing healthcare landscape by virtue of our commitment to being on the forefront of medical developments, legislative changes, and market trends.

DiseaseLandscape Insights is passionate about its goal of bringing forward positive change, enhancing patient outcomes, and fostering a healthy future as we move forward together. We are eager to engage with you, use our knowledge, and contribute to a better and healthier future for all.