Muscular Dystrophy: Causes, Symptoms, and Treatments

Muscular dystrophy is a group of disorders characterized by a progressive loss of muscle mass and consequent loss of strength.

The most common form of muscular dystrophy - Duchenne muscular dystrophy - typically affects young boys, but other variations can strike in adulthood.

Currently, there is no cure for muscular dystrophy, but certain physical and medical treatments can improve symptoms and slow the disease's progression.

This article will look at the diagnosis, symptoms, and treatments for muscular dystrophy, as well as examining current research into future treatments.

Contents of this article:

1. What is muscular dystrophy?
2. Symptoms
3. Causes
4. Diagnosis
5. Treatment
6. Current research

Fast facts on muscular dystrophy

Here are some key points about muscular dystrophy. More detail and supporting information is in the main article.

• Muscular dystrophy is a collection of muscle-wasting conditions
• Duchenne muscular dystrophy is the most common type
• A lack of a protein called dystrophin is the main cause of muscular dystrophy
• Gene therapies are currently being trialed to combat the disease
• There is currently no cure for muscular dystrophy

What is muscular dystrophy?

Muscular dystrophy causes the gradual weakening of skeletal muscle.

Muscular dystrophy is a muscle-wasting disease whose predominant forms may affect up to 1 in every 5,000 males.

The condition is caused by genetic mutations that interfere with the production of muscle proteins necessary to build and maintain healthy muscles.

The disease is genetic, and consequently, a history of muscular dystrophy in the family increases the chance of an individual developing the disease.

There are a number of muscular dystrophy types, including the following:

• Duchenne muscular dystrophy - the most common form of the illness. Symptoms normally start before a child's third birthday; they are generally wheelchair-bound by 12 and die of respiratory failure by their early-to-mid-twenties.
• Becker muscular dystrophy - similar symptoms to Duchenne but with a later onset and slower progression; death usually occurs in the mid-forties.
• Myotonic (Steinert's disease) - the myotonic form is the most common adult-onset form. It is characterized by an inability to relax a muscle once it has contracted. The muscles of the face and neck are often affected first. Symptoms also include cataracts, sleepiness, and arrhythmia.
• Congenital - this type can be obvious from birth or before the age of 2. It affects girls and boys. Some forms progress slowly whereas others can move swiftly and cause significant impairment.
• Facioscapulohumeral (FSHD) - onset can be at almost any age but is most commonly seen during teenage years. The muscular weakness often begins in the face and shoulders. People with FSHD may sleep with their eyes slightly open and have trouble fully closing their eyelids. When an individual with FSHD raises their arms, their shoulder blades protrude like wings.
• Limb-girdle - this variant begins in childhood or teenage years and first effects the shoulder and hip muscles. Individuals with the limb-girdle muscular dystrophy might have trouble raising the front part of the foot, making tripping a common problem.
• Oculopharyngeal muscular dystrophy - onset is between the ages of 40 and 70. Eyelids, throat, and face are first affected, followed by the shoulder and pelvis.

Symptoms of muscular dystrophy

Below are the symptoms of Duchenne muscular dystrophy, the most common form of the disease. The symptoms of Becker muscular dystrophy are similar but tend start in the mid-twenties or later, are milder, and progress more slowly.

Initial symptoms

• A waddling gait
• Pain and stiffness in the muscles
• Difficulty with running and jumping
• Walking on toes
• Difficulty sitting up or standing
• Learning disabilities, such as developing speech later than usual
• Frequent falls

Later symptoms

• Inability to walk
• A shortening of muscles and tendons, further limiting movement
• Breathing problems can become so severe that assisted breathing is necessary
• Curvature of the spine can be caused if muscles are not strong enough to support its structure
• The muscles of the heart can be weakened, leading to cardiac problems
• Difficulty swallowing - this can cause aspiration pneumonia, and a feeding tube is sometimes necessary

Causes of muscular dystrophy

Muscular dystrophy is caused by mutations on the X chromosome. Each version of muscular dystrophy is due to a different set of mutations, but all prevent the body from producing dystrophin. Dystrophin is a protein essential for building and repairing muscles.

Duchenne muscular dystrophy is caused by specific mutations in the gene that encodes the cytoskeletal protein dystrophin. Dystrophin makes up just 0.002 percent of the total proteins in striated muscle, but it is an essential molecule for the general functioning of muscles.

Dystrophin is part of an incredibly complex group of proteins that allow muscles to work correctly. The protein helps anchor various components within muscle cells together and links them all to the sarcolemma - the outer membrane.

If dystrophin is absent or deformed, this process does not work correctly, and disruptions occur in the outer membrane. This weakens the muscles and can also actively damage the muscle cells themselves.

In Duchenne muscular dystrophy, dystrophin is almost totally absent; the less dystrophin that is produced, the worse the symptoms and etiology of the disease. In Becker muscular dystrophy, there is a reduction in the amount or size of the dystrophin protein.

The gene coding for dystrophin is the largest known gene in humans. More than 1,000 mutations in this gene have been identified in Duchenne and Becker muscular dystrophy.7

Diagnosing muscular dystrophy

There are a variety of techniques used to definitively diagnose muscular dystrophy:

The genetic mutations involved in muscular dystrophy are well known and can be used to make a diagnosis.

• Enzyme assay - damaged muscles produce creatine kinase (CK). Elevated levels of CK in the absence of other types of muscle damage could suggest muscular dystrophy.
• Genetic testing - as genetic mutations are known to occur in muscular dystrophy, these changes can be screened for.
• Heart monitoring - electrocardiography and echocardiograms can detect changes in the musculature of the heart. This is especially useful for the diagnosis of myotonic muscular dystrophy.
• Lung monitoring - checking lung function can give additional evidence.
• Electromyography - a needle is placed into the muscle to measure the electrical activity. The results can show signs of muscle disease.
• Biopsy - removing a portion of muscle and examining it under a microscope can show the tell-tale signs of muscular dystrophy.

Treatment for muscular dystrophy

Currently, there is no cure for muscular dystrophy. Medications and various therapies help slow the progression of the disease and keep the patient mobile for the longest possible time.

Drugs

The two most commonly prescribed drugs for muscular dystrophy are:

• Corticosteroids - although this type of medication can help increase muscle strength and slow progression, their long-term use can weaken bone and increase weight gain
• Heart medications - if the muscular dystrophy impacts the heart, beta blockers and angiotensin-converting enzyme (ACE) inhibitors may be useful

Physical therapy

• General exercises - a range of motion and stretching exercises can help combat the inevitable inward movement of the limbs as muscles and tendons shorten. Limbs tend to become fixed in position, and these types of activities can help keep them mobile for longer. Standard low-impact aerobic exercises such as walking and swimming can also help slow the disease's progression.
• Breathing assistance - as the muscles used for breathing become weaker, it may be necessary to use devices to help improve oxygen delivery through the night. In the most severe cases, a patient may need to use a ventilator to breathe on their behalf.
• Mobility aids - canes, wheelchairs, and walkers.
• Braces - these keep muscles and tendons stretched and help slow their shortening. They also give added support to the user when moving.

Current research into muscular dystrophy

A great deal is known about the mechanisms of muscular dystrophy, both muscular and genetic, and although a full cure may be some distance away, there are avenues of research that draw ever closer to one.

Gene replacement therapy

Gene therapy is just one strand of research into treating muscular dystrophy.

Because the specific gene involved in muscular dystrophy has been found, a replacement gene that could create the missing dystrophin protein is a sensible consideration.

There are complicated problems with this approach, including the potential of the immune system to repel a new protein and the large size of the dystrophin gene needing to be replaced. There are also difficulties in targeting viral vectors directly to the skeletal muscle.

Another approach targets utrophin production. Utrophin is a protein similar to dystrophin that is not affected by muscular dystrophy. If utrophin production could be upregulated, the disease might be halted or slowed.

Altering protein production

If the dystrophin gene is being read by protein synthesis machinery and it reaches a mutation, it stops and does not complete the protein. Drugs are being trialed that cause the protein-making equipment to skip the mutated content and still continue to create dystrophin.

Drugs to delay muscle wasting

Rather than target the genes behind muscular dystrophy, some researchers are attempting to slow the inevitable muscle wasting.

Muscles, in standard circumstances, can repair themselves. Research into controlling or increasing these repairs could show some benefits for people with muscular dystrophy.

Stem cell research

Researchers are looking at the possibility of inserting muscle stem cells capable of producing the lacking dystrophin protein.

Current projects are looking at the most useful type of cells to use and ways in which they could be delivered to skeletal muscle.

Myoblast transplantation

During the early stages of muscular dystrophy, myoblasts (also called satellite cells) repair and replace faulty muscle fibers. As the myoblasts become exhausted, the muscles are slowly turned into connective tissue.

Some studies have attempted to insert modified myoblast cells into muscles to take over from the exhausted natural myoblasts.