MDA leads the search for treatments and therapies for Duchenne muscular dystrophy (DMD). The Association also provides comprehensive supports and expert clinical care for those living with DMD.
In this section, you’ll find up-to-date information about Duchenne muscular dystrophy, as well as many helpful resources. This information has been compiled with input from researchers, physicians and people affected by the disease.
As you learn more about DMD, always remember that you’re not alone. MDA is here for you and your family, standing ready to provide help and hope. There is a place for you in the MDA DMD community.
MDA provides support by:
Once you sign up with your local MDA office , you’ll begin receiving MDA’s quarterly Quest  magazine, where you’ll find news about research and health care, helpful products and devices, social and family issues, and more.
In addition, MDA will keep you informed through e-alerts, educational publications and speakers, seminars, videos and newsletters.
Please know that there’s a role for you in the fight against Duchenne muscular dystrophy. The MDA community is strong and dedicated, with opportunities for involvement at all levels, such as:
Please know that there’s an important role for every member of the DMD community. We urge you to contact your local MDA office  to learn more.
A DMD diagnosis doesn’t mean an end to your hopes and dreams. Changes, challenges and adaptations lay ahead, but also opportunity, fulfillment, joy and hope for a future free of Duchenne muscular dystrophy.
Never forget that MDA is here to help.
|In the early stages, Duchenne MD affects the shoulder and upper arm muscles and the muscles of the hips and thighs. These weaknesses lead to difficulty in rising from the floor, climbing stairs, maintaining balance and raising the arms.|
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. It is one of nine types of muscular dystrophy.
DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. Symptom onset is in early childhood, usually between ages 3 and 5. The disease primarily affects boys, but in rare cases it can affect girls.
Muscle weakness can begin as early as age 3, first affecting the muscles of the hips, pelvic area, thighs and shoulders, and later the skeletal (voluntary) muscles in the arms, legs and trunk. The calves often are enlarged. By the early teens, the heart and respiratory muscles also are affected. For more about DMD symptoms, see Signs and Symptoms .
Becker muscular dystrophy (BMD)  is a milder version of DMD. Its onset is usually in the teens or early adulthood, and the course is slower and less predictable than that of DMD.
Duchenne muscular dystrophy was first described by the French neurologist Guillaume Benjamin Amand Duchenne in the 1860s, but until the 1980s, little was known about the cause of any kind of muscular dystrophy. In 1986, MDA-supported researchers identified a particular gene on the X chromosome that, when flawed (mutated), leads to DMD. In 1987, the protein associated with this gene was identified and named dystrophin. Lack of the dystrophin protein in muscle cells causes them to be fragile and easily damaged.
DMD has an X-linked recessive inheritance pattern and is passed on by the mother, who is referred to as a carrier. For more about the way gene mutations cause Duchenne dystrophy, see Causes/Inheritance .
DMD carriers are females who have a normal dystrophin gene on one X chromosome and an abnormal dystrophin gene on the other X chromosome. Most carriers of DMD do not themselves have signs and symptoms of the disease, but a minority do. Symptoms can range from mild skeletal muscle weakness or cardiac involvement to severe weakness or cardiac effects and can begin in childhood or adulthood. For more, read Females and DMD  in Causes/Inheritance.
Until relatively recently, boys with DMD usually did not survive much beyond their teen years. Thanks to advances in cardiac and respiratory care, life expectancy is increasing and many young adults with DMD attend college, have careers, get married and have children. Survival into the early 30s is becoming more common, and there are cases of men living into their 40s and 50s. For more about living with DMD, see Medical Management .
MDA-supported researchers are actively pursuing several exciting strategies in DMD, such as gene therapy, exon skipping, stop codon read-through and gene repair. Human clinical trials are under way for some of these strategies. For an overview of DMD research strategies and the latest research news, see Research .
|Boys with DMD often have enlarged calf muscles.|
Children with Duchenne muscular dystrophy (DMD) are often late walkers.
In toddlers, parents may notice enlarged calf muscles (see image at right). This enlargement is known as pseudohypertrophy, or "false enlargement," because the muscle tissue is abnormal and may contain scar tissue.
A preschooler with DMD may seem clumsy and fall often. Parents also may note that children have trouble climbing stairs, getting up from the floor or running.
By school age, children may walk on their toes or the balls of their feet with a slightly waddling gait, and fall frequently. To try to keep their balance, they may stick out their bellies and pull back their shoulders. Children also have difficulty raising their arms.
Many children with DMD begin using a wheelchair sometime between ages 7 and 12. Transition to a wheelchair usually is a gradual process; at first, the chair may be required only to conserve the child's energy when covering long distances. (Children often experience renewed independence once they fully transition to a power wheelchair.)
In the teen years, activities involving the arms, legs or trunk may require assistance or mechanical support.
Because of weakened leg muscles, boys with DMD have a distinctive way of rising from the floor, called a Gowers’ maneuver.
They first get on hands and knees, then elevate the posterior, then “walk” their hands up the legs to raise the upper body.
The muscle deterioration in Duchenne MD isn’t usually painful in itself. Some people report muscle cramps at times; these usually can be treated with over-the-counter pain relievers.
Because muscular dystrophy doesn’t affect nerves directly, touch and other senses are normal, as is control over the smooth, or involuntary, muscles of the bladder and bowel, and sexual functions.
Lack of dystrophin can weaken the muscle layer in the heart (myocardium), resulting in a condition called cardiomyopathy. Over time, sometimes as early as the teen years, the damage done by DMD to the heart can become life-threatening. The heart should be monitored closely, usually by a pediatric cardiologist. See Medical Management  for more on cardiomyopathy in DMD.
Beginning at about 10 years of age, the diaphragm and other muscles that operate the lungs may weaken, making the lungs less effective at moving air in and out. Although the child may not complain of shortness of breath, problems that indicate poor respiratory function include headaches, mental dullness, difficulty concentrating or staying awake, and nightmares.
Weakened respiratory muscles make it difficult to cough, leading to increased risk of serious respiratory infection. A simple cold can quickly progress to pneumonia. It's important to get flu shots, and when infections occur, to get prompt treatment. See Medical Management  for more on respiratory care in DMD.
About a third of boys with DMD have some degree of learning disability, although few have serious mental retardation. Doctors believe that dystrophin abnormalities in the brain may have subtle effects on cognition and behavior. Learning problems in DMD occur in three general areas: attention focusing, verbal learning and memory, and emotional interaction.
Children suspected of having a learning disability can be evaluated by a developmental or pediatric neuropsychologist through the school system’s special education department or with a referral from the MDA clinic .
If a learning disability is diagnosed, educational and psychological interventions can begin right away. The specialist may prescribe exercises and techniques that can help improve these areas, and the school also can provide special help with learning. See Medical Management  for more about learning disabilities in DMD.
In diagnosing any form of muscular dystrophy, a doctor usually begins by taking a patient and family history, and performing a physical examination. Much can be learned from these, including the pattern of weakness. The history and physical go a long way toward making the diagnosis, even before any complicated diagnostic tests are done.
Early in the diagnostic process, doctors often order a blood test called a CK level. CK stands for creatine kinase , an enzyme that leaks out of damaged muscle. When elevated CK levels are found in a blood sample, it usually means muscle is being destroyed by some abnormal process, such as a muscular dystrophy or inflammation. A very high CK level suggests that the muscles themselves (and not the nerves that control them) are the likely cause of the weakness, although it doesn’t tell exactly what the muscle disorder might be.
Genetic testing involves analyzing the DNA of any cells (usually blood cells are used) to see whether there is a mutation in the dystrophin gene, and if so, exactly where it occurs. Such DNA testing for dystrophin mutations is widely available in the United States. Ask your MDA clinic  physician or genetic counselor for more information. And, for more on getting a definitive genetic diagnosis, see The Genie's Out of the Bottle: Genetic testing in the 21st century .
Female relatives of men and boys with DMD can undergo DNA testing to see if they are carriers of the disease. Women who are DMD carriers can pass on the disease to their sons and their carrier status to their daughters. In a minority of cases, girls and women who are DMD carriers may themselves show symptoms of DMD, such as muscle weakness and heart problems. These symptoms may not show up until adulthood. (See Causes/Inheritance .)
Several experimental drugs currently in development to treat DMD require knowledge of the person's precise genetic mutation, so genetic testing has become important not only for diagnosis but possibly for future treatments.
To obtain more information, the doctor may order a muscle biopsy , the surgical removal of a small sample of muscle from the patient. By examining this sample, doctors can tell a great deal about what’s actually happening inside the muscles.
Modern techniques can use the biopsy to distinguish muscular dystrophies from inflammatory and other disorders, and also to distinguish among different forms of muscular dystrophy. For instance, the amount of functional dystrophin protein found in a muscle biopsy sample sheds light on whether the disease course is likely to be DMD (with no dystrophin present) or the milder Becker muscular dystrophy  (with some partially functional dystrophin present).
|Muscles are made up of bundles of fibers (cells). A group of interdependent proteins along the membrane surrounding each fiber helps to keep muscle cells working properly. When one of these proteins, dystrophin, is absent, the result is Duchenne muscular dystrophy; poor or inadequate dystrophin results in Becker muscular dystrophy.|
|Diseases inherited in an X-linked recessive pattern mostly affect males, because a second X chromosome usually protects females from showing symptoms.|
Until the 1980s, little was known about the cause of any of the forms of muscular dystrophy. In 1986, MDA-supported researchers identified a gene on the X chromosome that, when flawed (mutated), causes both Duchenne and Becker  muscular dystrophies.
Genes contain codes, or recipes, for proteins, which are important biological components in all forms of life. In 1987, the protein associated with this gene was identified and named dystrophin.
DMD occurs because the mutated gene fails to produce virtually any functional dystrophin. (Individuals with Becker MD genetic mutations make dystrophin that is partially functional, which protects their muscles from degenerating as badly or as quickly as in DMD.)
DMD is inherited in an X-linked pattern, because the gene that can carry a DMD-causing mutation is on the X chromosome. Every boy inherits an X chromosome from his mother and a Y chromosome from his father, which is what makes him male. Girls get two X chromosomes, one from each parent.
Each son born to a woman with a dystrophin mutation on one of her two X chromosomes has a 50 percent chance of inheriting the flawed gene and having DMD. Each of her daughters has a 50 percent chance of inheriting the mutation and being a carrier. Carriers may not have any disease symptoms but can have a child with the mutation or the disease. DMD carriers are at risk for cardiomyopathy .
Although DMD often runs in a family, it's possible for a family with no history of DMD to suddenly have a son with the disease. There are two possible explanations:
The genetic mutation leading to DMD may have existed in the females of a family for some generations without anyone knowing it. Perhaps no male children were born with the disease, or, even if a boy in an earlier generation was affected, relatives may not have known what disease he had.
The second possibility is that the child with DMD has a new genetic mutation that arose in one of his mother’s egg cells. Since this mutation isn’t in the mother’s blood cells, it’s impossible to detect by standard carrier testing.
If a mother gives birth to a child with DMD, there’s always the possibility that more than one of her egg cells has a dystrophin gene mutation, putting her at higher than average risk for passing the mutation to another child. And once the new mutation has been passed to a son or daughter, he or she can pass it to the next generation.
A man with DMD can’t pass the flawed gene to his sons because he gives a son a Y chromosome, not an X. But he’ll certainly pass it to his daughters, because each daughter inherits her father’s only X chromosome. They’ll then be carriers, and each of their sons will have a 50 percent chance of developing the disease and so on.
A good way to find out more about the inheritance pattern in your family is to talk to your MDA clinic physician or a genetic counselor. More information is included in MDA’s booklet Facts About Genetics and Neuromuscular Diseases .
Why don’t girls usually get DMD? When a girl inherits a flawed dystrophin gene from one parent, she usually also gets a healthy dystrophin gene from her other parent, giving her enough of the protein to protect her from the disease. Males who inherit the mutation get the disease because they have no second dystrophin gene to make up for the faulty one.
Early in the embryonic development of a female, either the X chromosome from the mother (maternal X) or the one from the father (paternal X) is inactivated in each cell. The choice of which chromosome to inactivate is random. In each cell, there’s a 50 percent chance that either the maternal or paternal X chromosome will be inactivated, with the other left active.
Most of the time, it doesn’t matter how many inactivated maternal and paternal X chromosomes a female has. But when there’s a mutation in an X-chromosome gene, such as in the gene for dystrophin, it matters a lot.
If a girl or woman has to rely on too many X chromosomes with the dystrophin gene mutation (meaning the Xs with the functional dystrophin genes are mostly inactivated), she’s likely to develop symptoms of DMD or Becker MD.
Usually, however, girls don’t experience the full effects of DMD the way boys do, although they still have symptoms of muscle weakness. A minority of females with the mutation, called manifesting carriers, have some signs and symptoms of DMD.
For these women, the dystrophin deficiency may result in weaker muscles in the back, legs and arms that fatigue easily. Manifesting carriers may have heart problems, which can show up as shortness of breath or inability to do moderate exercise. The heart problems, if untreated, can be quite serious, even life-threatening.
In very rare instances, a girl may lack a second X chromosome entirely, or her second X may have sustained serious damage. In these cases, she makes little or no dystrophin (depending on the type of dystrophin mutation), and she develops DMD or BMD just as a boy would.
A female relative of a boy with DMD can get a full range of diagnostic tests to determine her carrier status. If she is found to be a DMD carrier, regular strength evaluations and close cardiac monitoring can help her manage any symptoms that may arise. For more on DMD in females, see Debatable Destinies: Duchenne muscular dystrophy carriers carry on, despite uncertainty .
Thanks to advances in many areas of medicine, such as cardiology and pulmonology, people with Duchenne muscular dystrophy in the 21st century are living longer than in previous decades, often well into adulthood. As of 2011, most therapies for DMD are supportive in nature, but research to develop truly disease-modifying therapies is under way.
The use of available treatments can help maintain comfort and function and prolong life. Talk with an MDA clinic  physician for more information.
People with DMD may have unexpected adverse reactions to certain types of anesthesia . It's important that the surgical team know about the patient's DMD so that complications can be avoided or quickly treated.
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Braces, also called orthoses, support the ankle and foot, or may extend up over the knee. Ankle-foot orthoses (AFOs) are sometimes prescribed for night wear to keep the foot from pointing downward and keep the Achilles tendon stretched while the child is sleeping.
Standing for a few hours each day, even with minimal weight bearing, promotes better circulation, healthier bones and a straight spine. A standing walker or standing frame  can assist people with DMD to stand. Some wheelchairs will raise the user into a standing position.
Sooner or later, a wheelchair is needed in DMD, typically by about age 12. Unless there's an injury, such as a broken leg, wheelchair use usually is gradual. Many at first use wheelchairs for long distances, such as at school or the mall, and continue to walk at home.
Although the child and parents may dread the wheelchair as a symbol of disability, most find that when they start to use one, they are actually more mobile, energetic and independent than when trying to walk.
Other mobility and positioning aids can help parents and caregivers. Among the simplest aid is a transfer board for helping the person move in and out of the wheelchair. Mechanical lifts , shower chairs  and electronic beds  also can be useful.
MDA's national equipment program  may be able to help families obtain some needed equipment.
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The American Academy of Pediatrics recommends that people with DMD have a complete cardiac evaluation by a specialist beginning in early childhood and again at least every other year until age 10. After that, the evaluations should be done every year or at the onset of symptoms of heart weakness, such as fluid retention or shortness of breath.
Female carriers of DMD  are at higher-than-average risk of developing cardiomyopathy. The academy suggests that carriers should undergo a complete cardiac evaluation in late adolescence or early adulthood, or sooner if symptoms occur, and that they should be evaluated every five years starting at age 25 to 30.
There’s some preliminary evidence that treatment with angiotensin converting enzyme (ACE) inhibitors and beta blockers can slow the course of cardiac muscle deterioration in DMD if the medications are started as soon as abnormalities on an echocardiogram (ultrasound imaging of the heart) appear but before symptoms occur.
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The impact of DMD can be minimized significantly by keeping the body as flexible, upright and mobile as possible. There are several ways to do this.
As muscle deteriorates, a person with muscular dystrophy often develops fixations of the joints, known as contractures. If not treated, these will become severe, causing discomfort and restricting mobility and flexibility. Contractures can affect the knees, hips, feet, elbows, wrists and fingers.
However, there are many ways to minimize and postpone contractures. Range-of-motion exercises , performed on a regular schedule, help delay contractures by keeping tendons from shortening prematurely. It’s important that a physical therapist show you how to do range-of-motion exercises correctly.
Braces on the lower legs also can help keep the limbs stretched and flexible, delaying the onset of contractures.
When contractures have advanced, surgery may be performed to relieve them. A tendon release procedure, also called heel cord surgery , is often done to treat ankle and other contractures while the child is still walking. Usually the boy will need to wear lower leg braces after this.
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No special dietary restrictions or additions are known to help in DMD. Most doctors recommend a diet similar to that for any growing boy but with a few modifications.
A combination of immobility and weak abdominal muscles can lead to severe constipation, so the diet should be high in fluid and fiber, with fresh fruits and vegetables dominant.
For boys who use power wheelchairs, take prednisone or who aren’t very active, excessive weight gain can become a problem. For these boys, caloric intake should probably be somewhat restricted to keep weight down. Obesity puts greater stress on already weakened skeletal muscles and the heart. Doctors have found that a low-calorie diet doesn’t have any harmful effect on the muscles.
Those on prednisone and those with heart problems may need a sodium-restricted diet.
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Exercise can help build skeletal muscle, keep the cardiovascular system healthy, and contribute to feeling better. But in muscular dystrophy, too much exercise could damage muscle. Consult with your doctor about how much exercise is best. A person with DMD can exercise  moderately but shouldn’t go to the point of exhaustion.
Many experts recommend swimming and water exercises (aquatic therapy) as a good way to keep muscles as toned as possible without causing undue stress on them. The buoyancy of the water helps protect against certain kinds of muscle strain and injury.
Before undertaking any exercise program, make sure to have a cardiac evaluation.
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Children with DMD who are suspected of having a learning disability can be evaluated by a developmental or pediatric neuropsychologist through the school system’s special education department or at a medical center with a referral from the MDA clinic .
If a learning disability is diagnosed, educational and psychological interventions can begin right away. The specialist may prescribe exercises and techniques, and the school also can provide special help with learning.
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Medications that lessen the workload on the heart are sometimes prescribed for DMD (See cardiac care , above).
Medications belonging to a group known as corticosteroids  have been found effective in slowing the course of DMD. The corticosteroids prednisone (available in the United States) and deflazacort (not usually available in the United States) are beneficial in the treatment of DMD.
Several high-quality studies of these medications in DMD showed a significant increase in strength, timed muscle function (such as the time it took to climb stairs) and pulmonary function.
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A physical therapy  program is usually part of the treatment for DMD. Your MDA clinic  physician will refer you to a physical therapist for a thorough evaluation and recommendations. The primary goals of physical therapy are to allow greater motion in the joints and to prevent contractures and scoliosis.
While physical therapy emphasizes mobility and, where possible, strengthening of large muscle groups, occupational therapy focuses on specific activities and functions. Occupational therapy can help with tasks for work, recreation or daily living, such as dressing or using a computer.
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As the muscles that assist in breathing get weaker, the bronchial system must be kept free of secretions, either by using a cough assist device or by manual assisted coughing with the help of a caregiver. A respiratory therapist or pulmonologist can be consulted for the needed information. At some point, assisted ventilation may be needed to help provide sufficient air flow into and out of the lungs.
The first step in using assisted ventilation is usually a noninvasive device , meaning one that doesn’t require any surgical procedures. The person receives air under pressure through a mask, nosepiece or mouthpiece. Noninvasive ventilation usually is required only part time, often only during sleep.
If round-the-clock ventilatory support becomes necessary, it’s possible to use noninvasive ventilation full time, under the care of a doctor knowledgeable in this practice. Some young men choose to switch to an invasive system, which means that a surgical opening called a tracheostomy  is performed, allowing air to be delivered directly into the trachea (windpipe).
For more, see:
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|Spinal curvatures are common in DMD, and many require surgical correction.|
In young men with DMD, the spine can be gradually pulled into a curved shape. The spine may curve from side to side (scoliosis) or forward in a “hunchback” shape (kyphosis).
Scoliosis usually appears after a boy has started using a wheelchair full time. The “swayback” curvature that's sometimes seen in those who are still walking is called lordosis.
Severe scoliosis can interfere with sitting, sleeping and even breathing, so measures should be taken to try to prevent it.
Exercises to keep the back as straight as possible and advice about sitting and sleeping positions can be obtained from a physical therapist.
Spine-straightening surgery  involves inserting metal rods with hooks into the spine.
Surgery for youngsters with DMD is usually performed in adolescence.
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General recommendations for medical care in DMD  were issued in 2009 by the DMD Care Considerations Working Group, under the auspices of the U.S. Centers for Disease Control and Prevention.
Guidelines for care of people with DMD receiving anesthesia or sedation  were released by the American College of Chest Physicians in 2007.
Recommendations for cardiovascular health supervision in BMD and DMD carriers  were issued in 2005 by the American Academy of Pediatrics.
Guidelines for respiratory care in DMD  were released by the American Thoracic Society in 2004.
Guidelines for the use of corticosteroids (prednisone or deflazacort) in DMD  also were released by the American Thoracic Society in 2004.
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MDA-supported investigators are actively pursuing several approaches to halt or reverse the muscle damage caused by Duchenne muscular dystrophy.
Some of the front-running strategies include: inserting new dystrophin genes; changing the way cells interpret genetic instructions; changing the mutated dystrophin gene itself; manipulating other proteins in the body to compensate for the lack of dystrophin; increasing blood flow to skeletal muscles and the heart; combating inflammation; and using stem cells to repair damaged muscles.
Some studies are focused on the dystrophin-deficient heart.
MDA's DMD Clinical Research Network is focused on advancing human clinical trials in this disease.
Researchers are pursuing a number of strategies to sustain or improve heart function in BMD and DMD. They're testing existing medications for their possible benefits in the BMD/DMD-affected heart, and conducting basic research to understand and find new approaches to treating the heart in these diseases.
Understanding and treating dystrophin-deficient cardiomyopathy  (cardiac muscle abnormalities) is a priority for MDA. The MDA DMD Clinical Research Network has made studying the natural history and treatment of this condition a primary focus. In addition, MDA sponsored a meeting of more than 40 leading clinicians and researchers from the United States and Europe in January 2011 to discuss optimal clinical care of the DMD/BMD-affected heart .
In 2009, scientists found that dystrophin gene mutations that cause cardiomyopathy in BMD  affect specific regions of the dystrophin protein, not necessarily the same regions associated with skeletal muscle loss. The study will allow better prediction of cardiomyopathy in BMD and earlier consideration of cardioprotective treatments in this disease, as well as giving researchers insight into which parts of the dystrophin protein are essential to preserve when shortened dystrophin molecules are being considered as therapeutic strategies.
The drug sildenafil (Viagra) has been found to impart cardioprotective effects in mice  with both an early- and late-stage DMD-like disease. Sildenafil, which is used to treat erectile-dysfunction, belongs to a class of drugs called phosphodiesterase 5 (PDE5) inhibitors, which relax the smooth muscles lining blood vessels, increasing blood flow to muscles and the heart. The cardiac effects of sildenafil in teens and men with DMD  are being studied.
Laboratory studies have found that an experimental compound designed to help seal cell membranes, p188, benefited heart function in dystrophin-deficient dogs .
In 2011, MDA-supported researchers found that inhibiting the action of a protein called NF-kappa B  improved cardiac function in mice with a severe DMD-like disease.
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Inflammation has been shown to be present in, and particularly harmful to, muscles affected by DMD. Scientists are working on understanding and interfering with inflammation in and around muscle fibers that may contribute to the DMD disease course.
Corticosteroids  (such as prednisone) are commonly are used in DMD to help preserve muscle strength and function. It's thought that they work, at least in part, by reducing inflammation. However, corticosteroids also cause unwanted side effects such as increased appetite, weight gain, loss of bone mass and cataracts.
It had been hoped that benefits might be maximized and side effects minimized by giving prednisone to people with DMD on a compressed, weekend-only schedule instead of daily. However, an MDA-supported study for which results were reported in 2011 found that the two prednisone schedules were about the same  with respect to benefit and side effects in this disease.
Some MDA-supported researchers are working on developing modified corticosteroids  that have fewer or less severe side effects than those currently in use.
An MDA-supported team reported in 2011 that the naturally occurring protein interleukin 10 (IL10)  may help reduce harmful inflammation and promote muscle regeneration in DMD and potentially in other forms of muscular dystrophy. These researchers conducted experiments in both cell culture and in a mouse model of DMD.
Other researchers have focused on the possible role of a protein called osteopontin in causing DMD-associated inflammation and scarring in muscles. In 2009, these researchers showed that eliminating osteopontin  was beneficial to mice with a DMD-like disease and concluded that reducing osteopontin should be investigated as a possible therarapy for DMD.
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Exon skipping is a strategy currently being developed for DMD (although it may have application to other genetic diseases down the line) in which sections of genetic code (exons) are “skipped,” allowing the creation of partially functional dystrophin, the muscle protein missing in DMD. Exon skipping is not a cure for DMD, but potentially could lessen the severe muscle weakness and atrophy that is the hallmark of this disease, making it more like Becker muscular dystrophy (BMD) .
Laboratory development of exon skipping began in the 1990s and has received significant funding from MDA since then.
Exon skipping uses molecules called antisense oligonucleotides to coax muscle fibers to ignore certain parts of the genetic instructions for dystrophin, thereby restoring the genetic "reading frame."
To understand this better, think of the genetic code for a protein as a sentence. Cells have to read the genetic “sentence” in units of three “letters” each.
Exon skipping is being tested in clinical trials in boys with DMD in the United States and in other countries.
In August 2011, AVI BioPharma, with supplemental support from MDA, began testing its exon-skipping drug eteplirsen  in boys with DMD still able to walk at Nationwide Children's Hospital in Columbus, Ohio. The pharmaceutical company GlaxoSmithKline began testing its exon-skipping drug GSK2402968  in nonwalking boys with DMD at the same hospital in 2010.
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Although still in very early stages of development, repair of the dystrophin gene  at the DNA level shows promise. This strategy is aimed at helping cells permanently repair errors in the dystrophin gene, fixing the underlying cause of DMD.
In experiments on cultured cells and in mice with flawed dystrophin genes, "designer" gene-repair molecules stimulated DNA repair levels more than 10 times greater than those achieved by a previous class of targeting molecules. The muscle cells containing rejuvenated dystrophin genes successfully produced normal dystrophin protein at levels consistently higher than muscle cells treated with the older-generation molecules.
Although the results so far have been encouraging, the frequencies of gene repair are in the 1 to 5 percent range — too low to be considered therapeutically relevant. And, for now, the gene repair strategy is limited to correcting "single-letter" errors (point mutations) in a gene.
Work must be done before this technique can progress to human trials, including refinement of the targeting molecules, studies to determine the most effective delivery methods and testing in different animal models.
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Gene therapy, or gene transfer, refers to the delivery of genes as therapeutic agents. Since genes carry the instructions for protein synthesis, they can lead to production of proteins that are directly or indirectly therapeutic in neuromuscular diseases. Because transferred genes potentially can continue to produce protein for some time, gene therapy may offer a more permanent fix than other therapies. But gene therapy faces many technical challenges, as well as a high bar set by regulatory agencies like the U.S. Food and Drug Administration (FDA).
The key challenges are delivering the genes to the targeted tissue while avoiding off-target tissues, and avoiding unwanted immune response to the proteins made from the new genes, or to the delivery vehicles in which the new genes are delivered.
MDA-supported scientists have created a miniaturized, working dystrophin gene that has been tested in boys with DMD. Although the treatment appeared to be safe, some of the boys experienced an unwanted immune response to the dystrophin protein  that limited the effectiveness of the gene transfer. This immune response is undergoing further investigation .
Blocking the myostatin protein via a protein called follistatin is a strategy that has potential for treating DMD and likely many other neuromuscular diseases. Mice with a DMD-like disease that received genes for the follistatin protein showed an overall increase in body mass and weight of individual muscles. Monkeys that received follistatin gene transfer  had stronger, larger muscles.
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Experiments have shown that, when dystrophin is missing from the muscle-fiber membrane, it causes another protein, known as nNOS, to be missing as well, and that this results in an inability of blood vessels supplying muscles to adequately dilate during exercise. When nNOS-deficient mice were treated with a phosphodiesterase inhibitor, which dilates blood vessels, their exaggerated fatigue response to exercise  was eliminated. Phosphodiesterase inhibitors are a class of drugs that include sildenafil (Viagra) and tadalafil (Cialis), both used to treat erectile dysfunction.
Other investigators found that treatment with sildenafil significantly improved heart function in mice missing the dystrophin protein.
On the basis of these and other findings, researchers have started investigating the possibility that phosphodiesterase inhibitors can improve skeletal-muscle or heart-muscle function in people with BMD or DMD.
In 2010, an MDA-supported trial testing the effects of tadalafil  on blood flow to muscles began in men with BMD.
Other trials of phosphodiesterase inhibitors also are under way to test their effects on skeletal-muscle and heart-muscle function in DMD and BMD.
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A strategy that has received considerable MDA support involves inhibiting the actions of a naturally occurring protein called myostatin , which limits muscle growth. Researchers hope that blocking myostatin may allow muscles to grow larger and stronger.
Inhibitors of myostatin have received much attention from the neuromuscular disease research community ever since it was found several years ago that people and animals with a genetic deficiency of myostatin appear to have large muscles and good strength without apparent ill effects. In 2010, a study showed that mice lacking dystrophin and showing a DMD-like disease benefited from treatment with a "decoy" that lured myostatin away from their muscles .
The biotechnology company Acceleron Pharma  then developed a drug based on this decoy and began testing it, with MDA support, in boys with DMD. Unfortunately, unexpected safety issues  arose during that trial, causing Acceleron to terminate it in 2011.
The company hopes to resolve these safety issues and resume testing ACE-031, or a modified version of ACE-031.
Other strategies to inhibit myostatin, such as injecting genes for the myostatin-blocking follistatin, also are under consideration.
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MDA scientists are using stem cells  (cells from which specialized cells "stem") isolated from muscle, blood vessels or bone marrow to regenerate muscles in dystrophin-deficient laboratory animals.
Stem cells are cells in the very early stages of development. They may be destined to turn into a specific cell type (such as muscle or nerve cells), or they may still retain pluripotency — the ability to develop into any of a number of different cell types.
In 2006, MDA-supported researchers restored mobility to two dogs and stabilized function in a third  using stem cells taken from muscle blood vessels.
In a study reported in 2007, a European research group successfully used a combination of genetic correction and stem cells to treat DMD research mice . The researchers in this study extracted muscle-generating stem cells from muscle tissue and blood in people with DMD, corrected the genetic error in the cells' dystrophin genes, and then injected the cells into dystrophin-deficient mice. The muscle-derived cells gave rise to better muscle regeneration than did the blood-derived cells.
In 2010, MDA-supported scientists in France reported they had identified a previously unknown type of muscle stem cell  located in the spaces between muscle fibers in mice. Although still in the early stages of research, it's hoped the new cells, dubbed PICs, may play an important a role in muscle regeneration and repair.
Scientists reported in 2010 that formation of new muscle tissue  first requires a controlled type of DNA damage. The new finding increases scientists' understanding of how immature muscle cells become muscle and could help them manipulate this process to treat several forms of muscular dystrophy.
Stem cells continue to be a major area of investigation for MDA-supported researchers. Some are continuing to study muscle satellite cells , a type of stem cell present in muscle tissue. Others are studying different cell types that are capable of surviving transplantation  into muscle and producing the desired proteins. Still, others are studying the similarities and differences in the development of skeletal muscle and fat tissue .
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In stop codon read-through, drugs target mutations known as premature stop codons (also called nonsense mutations), which tell the cell to stop making a protein — such as dystrophin — before it has been completely assembled. The drugs coax cells to ignore, or "read through," a premature stop codon in a gene.
A company called PTC Therapeutics , in conjunction with Genzyme Corp. , and with some initial funding from MDA, developed an experimental stop codon read-through drug called ataluren to treat DMD or Becker muscular dystrophy due to a premature stop codon. In October 2010, PTC announced that a lower dose of ataluren appeared to work better  than a higher dose. In a clinical trial, those on the lower dose walked an average of 29.7 meters (about 97 feet) more in six minutes than the high-dose or placebo groups (although all groups' walking distance declined over the course of the trial).
Another experimental drug designed to cause stop codon read-through in DMD is known as RTC13. In 2011, MDA gave a three-year grant to Carmen Bertoni at the University of California, Los Angeles (UCLA) to develop RTC13 so it can be taken orally. By the end of the trial, RTC13 is expected to cause a lot of muscle cells to ignore premature stop codon (nonsense) mutations and produce dystrophin, and improve symptoms in dystrophin-deficient mice with a DMD-like disease.
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Laboratory evidence shows that raising levels of the muscle protein utrophin can, to some extent, compensate for a deficiency of dystrophin.
Utrophin closely resembles dystrophin but, unlike dystrophin, is normally produced and entirely functional in BMD. Therefore, raising utrophin levels is unlikely to provoke an unwanted immune response, while raising levels of dystrophin may do so. Increasing utrophin production has the potential to help compensate for dystrophin deficiency regardless of the specific dystrophin gene mutation.
Although utrophin is close to dystrophin in both structure and function, there’s at least one key difference between the two proteins. During fetal development and perhaps a little beyond, utrophin is present all around the muscle fiber, interacting with clusters of proteins stuck in its surrounding membrane. As the animal or person matures, utrophin is replaced almost entirely by dystrophin, with one exception. At the neuromuscular junction, utrophin remains throughout life.
Several strategies are being tried to increase utrophin. One is to identify and suppress whatever is inhibiting utrophin production  — find the brake and release it, so to speak.
Another strategy is to inject a modified version of the utrophin protein  itself into the body. A 2009 study found that modified utrophin protein conferred significant benefits when injected into mice lacking the dystrophin protein and showing a disease resembling DMD.
Scientists reported in 2011 that systemically injecting the human form of a protein called biglycan  into mice with a disease resembling human DMD improved the resistance of mouse muscles to contraction-related damage; restored several proteins to their normal location at the muscle-fiber membrane; and recruited utrophin to the muscle-fiber membrane.
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Good science doesn't occur in isolation. The MDA DMD Clinical Research Network , consisting of five MDA-supported centers specializing in DMD research, is focusing on clinical trials in DMD, particularly research on heart problems and disease progression.
The network was established in August 2008, and by late 2010 had several clinical studies under way, such as a comparative study of treatments for heart disease in DMD  and studies to establish accurate criteria for measuring DMD progression  in children under 3 and in people with DMD who are no longer walking.
MDA clinics in the DMD network are located at the following sites (as of January 2013):
A clinical trial is a test in humans of an experimental medication or therapy. Clinical trials are experiments, not treatments, and participation requires careful consideration.
Although it's possible to benefit from participating in a clinical trial, it's also possible that no benefit — or even harm — may occur. Keep your MDA clinic  doctor informed about any clinical trial participation. (Note that MDA has no ability to influence who is chosen to participate in a clinical trial.)
For a more refined list of DMD clinical trials, visit ClinicalTrials.gov , a registry of federally and privately supported clinical trials in the United States and around the world. Select "Search for Clinical Trials," and follow the instructions to narrow down your search results.
|Suzan Norton, with her son, Mike|
When my husband, Terry, and I learned that our son Mike, then age 4, had Duchenne muscular dystrophy, we were devastated. Immediately, our hopes and dreams for Mike — playing sports, graduating high school, having girlfriends — all changed. That was 20 years ago.
I spent the next six months in chronic sorrow, but one day I woke up and knew we would be OK. We became involved with MDA and with other parents of children with DMD. Since then we’ve learned a great deal, much of it very hopeful. We have educated ourselves on being proactive with Mike’s care. Finding balance with siblings was sometimes difficult. Today, we’ve found inner peace with challenges facing us, and enjoy a full, rewarding family life.
It’s easy to become overwhelmed by your child’s diagnosis. But Terry and I assure you that you can cope with the emotional and physical tasks that lie ahead, if you take small steps, prioritize and listen to the needs of your family. Along the journey, you may sometimes be afraid, but your child will teach you many things, and you will learn to empower each other.
You may find others trying to set limits for your child. When Mike’s pediatrician asked about his participation in sports and my reply was negative, she asked why he didn’t play. Unknowingly, I had set limits on my son! Had it not been for that doctor, we would not have witnessed Mike’s love of baseball, which he played for three years.
We’ve been greatly helped by the information we’ve received from MDA and other families. These pages present an introduction to Duchenne MD designed to help you meet your child’s needs today and understand some of the changes to come.
From the information in this section, you’ll learn several encouraging things about muscular dystrophy: that your child’s diagnosis is not your “fault”… that DMD progresses over many years, giving your family time to adjust to changes…and that better treatments are constantly being developed for every aspect of the disease.
Society today is far more open to people with disabilities, and the law entitles your child to a full and inclusive education, employment opportunities and access to public places. Plus, there’s a whole world of technological devices to help your child do schoolwork, play and work. Currently, Mike is a student at college. Agencies such as our state vocational rehabilitation department have helped with access and provided him with voice-activated software. Not that long ago, isolation was an issue for disabled adults, but the Internet has changed all of that.
MDA’s website, as well as its social networking sites Facebook  and Twitter , help to keep parents connected, providing solutions to many problems and also emotional support all within minutes.
Surround yourself with inspirational and positive people. You will meet some amazing people along the way. Let your love for your child give you strength. Never give up your hopes and dreams. When our son graduated from high school, he had a girlfriend and was accepted by his peers. Today, he is comfortable in his own skin. He’s taught me more than I’ve taught him.
Through MDA, you’ll build a network of support. MDA’s Quest  magazine is filled with articles ranging from emergency room protocol, school issues, durable medical equipment and tips on buying a handicap van, as well as the latest research news. At your local MDA clinic , expert doctors and health professionals will answer questions and make referrals to other specialists. At your MDA support group , you’ll make friends and find understanding. And at MDA summer camp , your child will find a place to be independent, grow emotionally and have the time of his life.
Life will be about acceptance. After you get past your initial fear and devastation, you’ll find that life still holds many joys for your family. Twenty years have passed since the day of diagnosis. Our lives are full of laughter and adventure.
As you face the coming years, remember MDA and all its resources are there to help. May you have all the strength, hope and support you need. You are not alone.