MUSCULAR DYSTROPHY TREATMENT

Prevalence of Muscular Dystrophy

Epidemiologically, muscular dystrophy is relatively rare, aff ecting approximately 16 to 25 individuals per 100,000 people when considering all the diff erent types combined. The most common form in childhood is Duchenne muscular dystrophy, with an incidence of approximately 1 in 3500 live male births. On the other hand, myotonic dystrophy (DM1) is the most prevalent form in adults, estimated to have a point prevalence of 1 in 9400.

In India, qualitative genetic testing (TP-PCR) for DM1 is available and aff ordable. However, there is a lack of large cohort studies and phenotype-genotype correlations for this condition. In general, limb-girdle muscular dystrophies (LGMDs) have a worldwide prevalence rate ranging from 1 in 14,500 to 1 in 45,000, with the autosomal recessive (AR) forms being more common than the dominant ones.

In India, most studies on AR limb-girdle muscular dystrophies (ARLGMDs) are hospital-based and have limited genetic information. One notable study evaluated 300 cases at NIMHANS, Bangalore, over a period of 2 years (2010-2012). Out of these cases, 226 unrelated patients were confirmed to have muscular dystrophy based on biopsy, and 199 of them were classified into various ARLGMD subtypes using immunohistochemistry (IHC) and western blotting (WB) studies. Interestingly, dysferlinopathy (LGMD 2B) was found to be the most prevalent subtype (33.3%) in this study, which primarily recruited patients from the southern states of India, unlike western populations where calpainopathy (LGMD 2A) is reported as the most common subtype.

Congenital muscular dystrophies (CMD) constitute a rare group of muscular dystrophies that present in infancy or childhood. Their estimated prevalence is less than 0.89 per 100,000 individuals. In India, there is limited research on CMD, with only one study including 56 histopathologically confirmed cases.

Further research and awareness are crucial to better understand the epidemiology and genetic characteristics of muscular dystrophy in the Indian population, which can potentially aid in the development of more targeted and effective treatments.

There are several types of muscular dystrophy, each caused by specific genetic mutations:

1. Duchenne Muscular Dystrophy (DMD): This is the most common type and is caused by mutations in the dystrophin gene. It is inherited in an X-linked recessive pattern
2. Becker Muscular Dystrophy (BMD): Similar to DMD, BMD is caused by mutations in the dystrophin gene, but it is less severe. It is also inherited in an X-linked recessive pattern.
3. Congenital Muscular Dystrophy (CMD): This type presents at birth or early infancy and is caused by various genetic mutations. It can have different inheritance patterns, including autosomal recessive for some subtypes.
4. Myotonic Muscular Dystrophy (DM): This type is characterized by muscle stiffness (myotonia) and is caused by mutations in specific genes. It can be inherited in an autosomal dominant pattern.
5. Limb-Girdle Muscular Dystrophy (LGMD): LGMD includes several subtypes, and it is caused by mutations in various genes. It can be inherited in both autosomal recessive and dominant patterns.
6. Facioscapulohumeral Muscular Dystrophy (FSHD): FSHD is characterized by weaknessin the face, shoulders, and upper arms. It is caused by mutations in specific genes and is typically inherited in an autosomal dominant pattern.

Etiology of Muscular Dystrophy

The cause of muscular dystrophy is attributed to mutations in genes responsible for healthy muscle structure and function. These mutations lead to the impairment of muscle maintenance and result in progressive muscle weakness over time.

The inheritance pattern varies depending on the specific type of muscular dystrophy:

• Recessive inheritance: Both biological parents pass on a genetic mutation causing the condition. This type is seen in Limb-Girdle Muscular Dystrophy and Congenital Muscular Dystrophy.
• Dominant inheritance: Only one biological parent needs to pass on the mutated gene for the individual to develop the condition. Myotonic, Facioscapulohumeral, and Oculopharyngeal muscular dystrophies have this type of inheritance.
• Sex-linked (X-linked) inheritance: This type affects genetically male individuals (one X and one Y chromosome). Duchenne and Becker muscular dystrophies are examples of X-linked inheritance.

In rare cases, a person may develop muscular dystrophy due to a de novo mutation, meaning the mutation occurred randomly and was not inherited from the parents.

Underlying Mechanisms of Muscular Dystrophy

The pathophysiology of muscular dystrophy involves a complex interplay of multiple proteins that play crucial roles in muscle membrane stability and interactions with the extracellular environment. Among these proteins, dystrophin and the dystrophin-associated glycoproteins (DAGs) are particularly important for sarcolemmal stability.

The dystrophin gene is situated on the short arm of the X chromosome and is responsible for coding the large protein Dp427. Although dystrophin constitutes only about 0.002% of the proteins in striated muscle, it plays a crucial role in maintaining the integrity of the muscle’s membrane.

Dystrophin forms a stable complex by aggregating as a homotetramer at the costomeres in skeletal muscles. Additionally, it associates with actin at its N-terminus and with the DAG complex at the C-terminus, facilitating interactions with laminin in the extracellular matrix. In cases where dystrophin is lacking, cellular instability occurs at these connections, leading to progressive leakage of intracellular components, resulting in elevated levels of creatine phosphokinase (CPK) commonly seen in routine blood workup of patients with Duchenne muscular dystrophy (MD).

In conditions like Becker muscular dystrophy, less active forms of dystrophin may still serve as a sarcolemmal anchor, but they may not be as effective in regulating the flow of intracellular substances, leading to some leakage. Both Duchenne and Becker MD involve the gradual degeneration of muscle-cell units with macrophage invasion. Although the damage in MD is not typically associated with immunological mechanisms, the presence of class I human leukocyte antigens (HLAs) on the membrane of dystrophic muscles makes them more susceptible to T-cell mediated attacks.

Research using selective monoclonal antibody hybridization has identified cytotoxic T cells as the invading macrophages, and complement-activated membrane attack complexes have also been detected in dystrophic muscles. Over time, the deceased muscle tissue is replaced by a fibrofatty infiltrate, clinically presenting as pseudohypertrophy of the muscle. The lack of functioning muscle units leads to weakness and eventual contractures.

Other types of muscular dystrophies result from alterations in the coding of one of the DAG complex proteins. The gene loci coding for these DAG complex proteins are located outside the X chromosomes. Defects in these proteins lead to changes in cellular permeability. However, due to differences in the mechanism of action and locations of these gene products within the body, other associated effects are observed, such as in ocular and limb-girdle type dystrophies.

Regarding genetic defects and dystrophin, X-linked forms of MD like Duchenne and Becker dystrophies involve a defect in the X chromosome’s short arm at site Xp21 region, encompassing about 2 million base pairs. The gene codes for Dp427, an essential component of the cytoskeleton of the cell membrane.

Dystrophin is present not only in skeletal muscle but also in smooth and cardiac muscles as well as in the brain. The large size of the dystrophin gene explains why spontaneous new mutations, as seen in Duchenne MD, can occur more easily. This size also allows mistakes in protein synthesis to happen at multiple sites.

Defects that interfere with the translation reading frame or the promoter sequence initiating dystrophin synthesis lead to an unstable and ineffective protein, as in Duchenne MD. Disruption of the translation process further downstream results in the production of lower molecular weight proteins, which, although present, are less active and contribute to the milder Becker MD phenotype.

In conditions like limb-girdle MD, which is autosomal recessive, the genetic defect is localized to the 13q12 locus. In autosomal dominant facioscapulohumeral MD, the defect is found at the 4q35 locus, while in distal MD, it is located at the 2q12-14 loci.

Manifestations of Muscular Dystrophy

The symptoms of muscular dystrophy can vary depending on the specific type, but the common feature is muscle weakness and related issues.

The progression of symptoms typically worsens over time. Some of the muscle- and movement-related symptoms include muscle atrophy, repeated falls, difficulty walking, climbing stairs, or running.

A characteristic feature, known as the Gower manoeuvre, is observed as children use their hands to push themselves up from the ground. Weakness in girdle muscles and initial calf hypertrophy may also be seen.
Muscular dystrophy can cause an irregular walking gait, such as waddling or toe walking, and may lead to stiffor loose joints.

Contractures, where there is permanent tightening of muscles, tendons, and skin, can occur. Spasticity and muscle pain are also common symptoms.

Other symptoms that can be associated with muscular dystrophy include fatigue, trouble swallowing (dysphagia), heart problems like arrhythmia and cardiomyopathy, scoliosis (curved spine), breathing difficulties, and intellectual disabilities. Learning disorders may also be present in some cases.

It’s important to note that the specific symptoms and their severity can vary depending on the type of muscular dystrophy an individual has. Early diagnosis and management are essential to provide appropriate care and support for affected individuals. Regular monitoring and intervention by healthcare professionals can help improve the quality of life for those with muscular dystrophy.

Diagnostic Evaluation for Muscular Dystrophy

When investigating muscular dystrophy, several tests and procedures are used to aid in the diagnosis and assessment of the condition. Some of the common investigations include:

1. Blood tests: Blood tests are conducted to measure the levels of certain substances that may indicate muscle weakness, injury, or disease. Elevated levels of these substances can provide valuable information and may prompt further testing. Some of the substances measured in blood tests include serum creatine kinase, serum aldolase, and myoglobin.
2. Muscle biopsies: In this procedure, a small piece of muscle tissue is removed using a needle or small incision. The collected tissue is then examined under a microscope to identify characteristic features of muscular dystrophy. Muscle biopsies can help confirm the diagnosis and provide additional insights into the specific type of MD. Genetic testing is often performed alongside muscle biopsies to confirm the presence of specific gene mutations.
3. Genetic testing: Genetic testing is crucial in diagnosing muscular dystrophy as it helps identify genes known to cause or be associated with inherited muscle diseases. DNA analysis and enzyme assays can confirm the presence of certain neuromuscular diseases, including MD.
4. Neurological tests: These tests are conducted to rule out other nervous system disorders and to assess muscle weakness, reflexes, coordination, and contractions. They help in identifying patterns of muscle weakness and wasting.
5. Heart testing: Some forms of MD can affect the heart, causing irregular heartbeats or cardiomyopathy. Heart testing, such as an electrocardiogram (ECG) or echocardiogram (Echo), is performed to assess heart rate, rhythm, and structure.
6. Exercise assessments: These assessments are used to measure the patient’s muscle strength and breathing. They can help detect any increased markers following exercise, which may provide valuable information about muscle function.
7. Imaging tests: Magnetic resonance imaging (MRI) and ultrasound imaging are used to examine muscle quality, bulk, and fatty replacement of muscle tissue. These imaging tests can provide visual information about the muscles and aid in the diagnosis and monitoring of muscular dystrophy.

These investigations collectively help in diagnosing and understanding the type and severity of muscular dystrophy in an individual. Early and accurate diagnosis is essential for effective management and treatment planning to improve the quality of life for those affected by muscular dystrophy.

NAMMA HOMEOPATHY MANAGEMENT

NAMMA HOMEOPATHY takes a comprehensive approach to manage Muscular Dystrophy, which is a group of hereditary muscle-destroying disorders with varying characteristics. It affects the skeletal muscles, leading to progressive weakness and degeneration. Unfortunately, many people are unaware of this condition and receive only symptomatic treatment, which is often inadequate as the disease rapidly progresses, leading to wheelchair-bound patients by the age of 12.

NAMMA HOMEOPATHY aims to improve the quality of life for individuals with Muscular Dystrophy and has introduced a new formula called MORBIFIED GENOMIC DYNAMIS, which shows promising results in treating this genetic disease. The disorder primarily affects the chromosomes, causing alterations in the production of the protein dystrophin, leading to muscle weakness and degeneration.

The new formulated Namma Homeopathic medicine is designed to slow down the process of muscular degeneration and improve muscle power by modulating the mutated gene. To provide personalized treatment, Namma Homeopathic medicines are prescribed after conducting a detailed case study, which includes considering the physical, emotional, and genetic makeup of each individual. The medical history of the mother’s pregnancy and any family history of the disease is also examined to address the root cause of the condition.

In addition to medication, NAMMA HOMEOPATHY emphasizes the importance of physical therapy, exercise, and proper diet and regimen. They may also recommend the use of orthopedic instruments such as wheelchairs and standing frames to preserve muscle function and prevent joint contractures. By adopting a holistic and personalized approach, NAMMA HOMEOPATHY aims to provide effective management and support for individuals with Muscular Dystrophy.