Duchenne Muscular Dystrophy
Muscular dystrophies is basically a condition that is characterized by muscle weakness and degeneration. As for duchenne muscular dystrophy, the muscular dystrophy is characterized by the enlargement of muscles. The muscle tissue is slowly replaced by fat tissue which gives it its enlarged appearance. Duchenne muscular dystrophy is one of the most prevalent types of muscular dystrophy and is characterized by rapid progression of muscle degeneration that occurs early in life. Duchenne muscular dystrophy conditions are caused by a mutation in the same gene and usually affect only boys.
Duchenne muscular dystrophy is named after a French neurologist, who went by the name of Guillaume B. A. Duchenne, who first described the disorder in 1861 (2007). To be precise, “In 1868, he gave a comprehensive account of 13 patients with the disease, which he called "paralysie musculaire pseudo-hypertrophique" (Do, 2012). Current understanding of Duchenne muscular dystrophy is due to the work of the American geneticist, named Elizabeth Shull Russell. In 1951, Russell accidentally observed symptoms of duchenne muscular dystrophy in a colony of mice with which she was experimenting on. In fact, “Over a period of years, she was able to show that this form of muscular dystrophy is inherited as an X-linked recessive trait” (World of Scientific Discovery, 2007). This makes it a hereditary condition that is passed on.
The first symptoms of Duchenne muscular dystrophy are usually noticed in early childhood. Delays in developmental milestones such as walking and sitting are common. The affected child often stumbles during mobility, and running requires difficult effort. Muscular dystrophy often is not suspected until additional signs are apparent. By the age of four to five years, the diagnosis is usually made. As previously stated, the muscles are enlarged during this condition. In fact, “Although some muscles, such as the calves, appear to be large and defined, the muscle is actually atrophied and weak. It appears large because deposits of fatty, fibrous tissue are replacing muscle tissue” (Bosworth, 2010). This results in early signs of weakness, where mobility is difficult, progressing to the point that the affected boy is unable to walk. Boys with Duchenne muscular dystrophy usually require wheelchairs by the age of 12 years and eventually the muscles that support the neck are affected. With duchenne muscular dystrophy, usually skeletal muscles are affected first, then progresses to the cardiac muscles. Weak, abnormal cardiac muscles cause breathing difficulties and heart problems for the patients. Breathing difficulties lead to different lung infections, such as pneumonia (2010). These problems are fatal in duchenne muscular dystrophy. This leads to the life expectancy for a boy with Duchenne muscular dystrophy is the late teens or early twenties.
The diagnosis of muscular dystrophy, “is based on acquiring physical symptoms, family history, muscle biopsy, measurement of creatine kinase, and genetic testing. Creatine kinase may also be called creatine phosphokinase. It is a protein present in skeletal muscle, cardiac muscle, and the brain” (Bosworth, 2010). Creatine kinase is an enzyme found in most muscles as well as the brain. Damage to muscles results in release of creatine kinase into the blood. The level of creatine kinase in the blood is increased if a person has muscular dystrophy. The level in a male with duchenne muscular dystrophy is often more than ten times the normal level. Another procedure is a muscle biopsy in which a piece of muscle tissue is removed from an organism and examined. Early in the course of the disease, the muscle shows general abnormalities. Later in the disease, the muscle tissue appears even more abnormal than before. The fat and fibrous tissues that are replacing the muscle fibers are becoming visible. One more new, innovative way is genetic testing (2010). Genetic testing is a useful diagnostic tool because the diagnosis can be made without an invasive muscle biopsy where tissue must be extracted. Blood from the person suspected to have muscular dystrophy is extracted and analyzed at a specialty laboratory. Genetic testing will confirm if the selected gene is abnormal for most males affected with muscular dystrophy.
Causes of duchenne muscular dystrophy are in the mutations in the DMD gene. Because the DMD gene is on the X chromosome, duchenne muscular dystrophy affects only boys. Most females have two X chromosomes so if a female inherits an X chromosome with a mutation in the DMD gene, she has another normal DMD gene on her other X chromosome that protects her from developing symptoms. Though, this makes the woman a carrier. The DMD gene provides instructions for a protein called dystrophin. Mutations in DMD associated with Duchenne often completely disrupt production of dystrophin, such that no dystrophin is present. Dystrophin is part of muscle cells and some nerve cells. Its function is not entirely understood. It is believed that, “Based on its location in the muscle cell, scientists think that dystrophin may help maintain the structural integrity of muscle cells as they contract” (World of Scientific Discovery, 2007). Dystrophin and the associated proteins form a complex system that connects the intracellular cytoskeleton to the extracellular matrix. Also, “The normal operation of this system is critical for maintaining the integrity of the delicate, elastic muscle membrane (sarcolemma) and the muscle fiber. The responsible gene is located on the short arm of the X chromosome at locus Xp21” (The Gale Encyclopedia of Science, 2008). People with duchenne muscular dystrophy make very little or no dystrophin. When there is not enough dystrophin in the muscle, it becomes weak and starts to waste away.
There is currently no cure for this condition. Treatment aims to control symptoms to improve the patient's life. Steroid rugs can slow the loss of muscle strength. This may start when the child is diagnosed or when muscle strength begins to decline. An important step forward in understanding and possibly treating duchenne muscular dystrophy occurred in 1986 when scientists at Harvard Medical School discovered that the defective gene responsible for DMD is located on the short arm of the X chromosome. They found that the protein produced by the normal gene, dystrophin, is absent from the cells of DMD patients. One consequence of this discovery was a 1989 research project in which mice with a defective DMD gene were treated with immature muscle cells. The new muscle cells apparently contained correct copies of the gene and began producing dystrophin in normal amounts (2010). In the twenty-first century, gene therapy has come apparent to the therapeutic approach for muscular dystrophy, especially now that scientists have identified the mutated genes that can cause Duchenne and other muscular dystrophies. For example, researchers have developed an artificial dystrophin gene to replace the absent protein in Duchenne muscular dystrophy, and research is ongoing into how to best deliver copies of these genes into muscle cells so that they work efficiently and continue to function. In 1998, researchers also showed that genes containing the muscle protein sarcoglycan can correct defects in muscular dystrophy. They conducted the experiment where the genes were injected into the leg muscles of hamsters and immunosuppressive drugs were used (2010). Immunosuppressive drugs are drugs that inhibit or prevent activity of the immune system. The use of these drugs during gene therapy research using artificial proteins has proven to be a major barrier to gene therapy. This is because suppressing the immune system can make the patient susceptible to other diseases because of their function, and immunosuppressive drugs have many potentially serious side effects. In addition to opening up a new waypoint for new therapies, research into the genetics of muscular dystrophy is helping scientists to better understand the disease itself. In other cases, some types of muscular dystrophy thought to be one disease are now known to be different diseases caused by various genetic defects. As research continues, revelations are being made as the scientific world learns more and more about the shifts occurring in our bodies.