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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Scientists around the globe are conducting intense research  to understand what causes muscle dysfunction in Duchenne muscular dystrophy (DMD) and to apply that understanding to the development of effective treatments. Since inception, MDA has dedicated over $209 million to DMD research, with over $45 million of that investment coming in the past five years alone. The research efforts of thousands of scientists over the course of decades has resulted in many promising leads for potential therapies , some of which are currently being evaluated by the FDA  for approval.
In DMD, the muscle is missing a key structural protein called dystrophin, making it more susceptible to injury. Eventually the body can’t keep up with repair, which leads to muscle loss and weakness. Scientists therefore are working hard on the development of a number of complementary therapies that could replace dystrophin, protect the muscle from injury and/or promote muscle repair and regrowth. Doctors hope that someday these potential therapies may be used in combination for maximum benefit.
Some of the front-running strategies discussed in this section include:
Many examples of these potential therapies already have advanced into clinical trials where they are being evaluated for benefits in people with DMD. See the DMD Clinical Trial Feed  for a list of clinical trials currently being conducted for DMD.
MDA also has created a dedicated DMD Clinical Research Network  that aims to advance human clinical trials in this disease.
Gene therapy, or gene transfer, refers to the delivery of genes as therapeutic agents. It is being developed in a wide range of disease areas because it has the potential to deliver healthy replacement genes to anyone with a gene mutation, or to deliver adjunct genes (sometimes called “surrogate” gene therapy) that can alleviate disease symptoms.
For gene therapy in DMD, a primary goal is to deliver a replacement copy of the dystrophin gene. Scientists hope that by introducing a functional dystrophin gene, gene therapy may offer a more permanent benefit than other therapies, but they are quick to caution that gene therapy for DMD is unlikely to completely halt or reverse the disease.
To accomplish gene transfer in DMD, some researchers aim to utilize the action of viruses. A virus works by inserting its own genetic material into a host, which causes the host’s cells to manufacture viral proteins and create more virus (and in doing so, elicits an immune response that makes the host “sick”). But researchers believe it may be possible to swap out the viral genes for a dystrophin gene, which will trick the virus into delivering the dystrophin gene to people with DMD where the person’s muscle cells will use it to manufacture dystrophin protein. To accomplish this without making the patient sick, scientists are utilizing viruses that do not cause illness in humans.
Research into the development of gene therapy for DMD is robust, but some challenges remain. The key difficulties researchers are working to overcome include dealing with the large size of the dystrophin gene, delivering a sufficient quantity of the new genes to muscle (while avoiding other tissues), and avoiding an unwanted immune response to the proteins made from the new genes.
The large size of the dystrophin gene poses a challenge because gene therapy relies on engineered viruses, and there is a limit to the size of the load that these viruses can carry. To address this, MDA-supported scientists have created smaller, but still functional, versions of dystrophin to use in gene therapy. Mini-dystrophin (rAAV2.5-CMV-minidystrophin) is a miniaturized, working dystrophin gene that has been tested in boys with DMD. At the end of clinical testing, scientists determined that the treatment was safe, but unfortunately some of the boys experienced an unwanted immune response to the dystrophin protein . This immune response prevented the newly synthesized mini-dystrophin protein from being used properly by muscle cells, and thereby limited the effectiveness of this approach.
Several research groups are now working toward the development of an even smaller version of dystrophin, called micro-dystrophin. Micro-dystrophin contains the minimum amount of information from the dystrophin gene needed to produce a functional protein. The most advanced of these therapies, rAAVrh74.MCK.Micro-Dystrophin, is being developed by a team at Nationwide Children’s Hospital and currently is undergoing phase 1 clinical testing in boys with DMD.
To address delivery of genes specifically to muscles (while avoiding other tissues), researchers have introduced a muscle specific promotor that functions like a control switch for the new dystrophin gene. Muscle specific promoters selectively promote activation of the gene in the muscle, but in other tissues the gene remains dormant so it cannot create unwanted side effects. Researchers led by Dr. Jerry Mendell are developing gene therapies that are activated by the muscle-specific promotor muscle creatine kinase (MCK). Potential therapies that utilize muscle specific promoters are currently in phase 1 clinical testing for DMD (rAAVrh74.MCK.micro-Dystrophin) and also phase 1-2 testing for LGMD (scAAVrh74.tMCK.hSGCA).
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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 (AONs) 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. Two of these therapies, eteplirsen  and drisapersen , have completed clinical testing in the US and are currently being evaluated by the FDA  for approval.
In August 2011, Sarepta Therapeutics (then known as AVI BioPharma), with supplemental support from MDA, began testing its exon 51-skipping drug eteplirsen  in boys with DMD still able to walk at Nationwide Children's Hospital in Columbus, Ohio. Having completed clinical testing, eteplirsen is currently being evaluated by the FDA for approval. In 2010, the pharmaceutical company GlaxoSmithKline began testing its exon-51 skipping drug GSK2402968  in nonambulatory boys with DMD at the same hospital. GSK2402968, purchased by BioMarin Pharmaceutical Inc., and now called drisapersen, has since completed clinical testing. BioMarin has also applied to the FDA in 2015 for approval of drisapersen. Both eteplirsen and drisapersen target exon 51, and may therefore benefit up to 13 percent of people with DMD.
Additionally, drugs aimed at skipping of exons 45 (BMN 045, SRP-4045) and 53 (BMN 053, SRP-4053, and NS-065/NCNP-01 in Japan) are currently in clinical development, and many more potential therapies are in preclinical development (for skipping of exons 8, 44, 50, 52 and 55, among others).
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Stop codon read-through
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. Between 5-10 percent of people with DMD have premature stop codon/nonsense mutations and may therefore someday benefit from read-through therapies.
A company called PTC Therapeutics , in conjunction with Genzyme Corp. , and with 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 those in the high-dose or placebo groups (although all groups' walking distance declined over the course of the trial). Ataluren (Translarna), now owned wholly by PTC, will soon be evaluated by the FDA for approval in the US. It is currently available to DMD patients in the EU .
Researchers at a company called Nobelpharma have developed another stop codon read-through therapy called NPC14. This potential therapy may function similarly to Ataluren and is currently undergoing clinical testing in Japan.
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A prominent symptom of DMD is loss of muscle, so researchers aim to develop therapies that promote regrowth of muscle and, in turn, increase muscle strength.
One strategy that has received considerable MDA support involves inhibiting the actions of a naturally occurring protein called myostatin  that limits muscle growth. In healthy muscle, myostatin performs an important role: it pushes back against growth signals to maintain muscle at a reasonable size. But in DMD, where muscle loss contributes to a decline in function, myostatin exacerbates the problem. Thus, researchers hope that blocking myostatin may allow DMD muscles to grow larger and stronger.
Inhibitors of myostatin have received much attention from the neuromuscular disease research community since it was found years ago that people and animals with a genetic deficiency of myostatin appear to have large muscles and good strength without apparent ill effects.
Initial efforts to develop therapies based on myostatin inhibition did not bear out. In 2008 a therapy called MYO-029 (developed by Wyeth) failed to meet its endpoint during a clinical trial of people with a variety of dystrophies, though not including DMD. Additionally in 2011, a DMD trial with ACE-031, which was developed by Acceleron Pharma, had to be discontinued due to safety concerns. Although these myostatin inhibitors were not successful, much was learned from these efforts.
Currently, Pfizer is developing a myostatin inhibitor called PF-06252616, which is in clinical trials to test its effectiveness in DMD boys. Bristol-Myers Squibb is also developing a myostatin inhibitor drug, BMS-986089. This potential therapy is currently in a phase 1/2 study to determine its safety in DMD boys. In addition to these two potential DMD medicines, Eli Lilly (LY2495655), Regeneron (REGN1033) and Novartis (BYM338) are also developing drugs that inhibit myostatin, but these are being tested in clinical studies for their effects in cancer wasting (cachexia), sarcopenia and inclusion-body myopathy (IBM) , respectively.
Another unique strategy to block the action of myostatin uses gene therapy to introduce follistatin, a naturally occurring inhibitor of myostatin. 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. Furthermore, monkeys that received follistatin gene transfer  had stronger, larger muscles. A gene therapy for delivering follistatin to people with DMD called rAAV1.CMV.huFollistatin344 is currently being developed by Milo Biotechnology. This potential therapy is now being tested in an early-stage (phase 1) clinical trial.
Researchers are also exploring the possibility of inducing muscle growth in DMD patients through activation of androgen receptors using drugs called Selective Androgen Receptor Modulators (SARMs). Androgen receptors bind to testosterone and other steroids to induce muscle growth, but anabolic steroids cause many undesirable side effects.
SARMs may offer a way to reap the benefits of muscle androgen mediated growth but with fewer side effects. The drug DT-200 is an oral SARM in development by Akashi Therapeutics, and has shown positive effects in early studies. Akashi next aims to study the safety of this compound in a clinical trial with healthy volunteers. Their long-term plan is to develop DT-200 for treatment of DMD.
A second company called GTx Inc. also is developing SARMs for a variety of muscle wasting conditions, including muscular dystrophy and cancer. Their DMD program is in the preclinical development phase.
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Stem cell transplantation
In DMD, muscle is more susceptible to injury because it is missing the dystrophin protein. The muscle will continually work to repair itself, but will eventually fall behind. So scientists hope to accelerate repair by transplanting stem cells into DMD muscle.
Stem cells  are normally present in a variety of tissues, including muscle, where they play a crucial role in repair and maintenance. Stem cells can be thought of as cells that are in the very early stages of development, before they have become specialized (differentiated) to perform specific roles in tissues. They may be precursors to 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 adults and children, stem cells reside in muscle tissue where they remain dormant until the tissue is damaged by injury or disease. Following tissue damage, stem cells become activated and then serve to replenish the damaged tissues. For treatment of DMD, then, scientists hope that stem cells could someday be transplanted (from healthy donors) to grow new muscle.
One type of stem cell that holds a lot of promise for transplant is called induced pluripotent stem cells (iPS cells). These cells are derived from adult cells in a process that was pioneered by Dr. Shinya Yamanaka ’s lab in Japan . In 2012 he was awarded the Nobel Prize for this work. Building off of this breakthrough, MDA-supported scientists led by Dr. Radbod Darabi have demonstrated that human skin-derived iPS cells are able to differentiate into muscle and can be successfully transplanted  into mice that model DMD. The mice are able to accept the new cells, and the cells produce the dystrophin protein.
A team of MDA-supported scientists led by Dr. Rita Perlingeiro have invented and continue to refine a method to efficiently generate immature skeletal muscle cells from iPS cells . In addition, they have shown that, once transplanted, the cells integrate with existing skeletal muscle cells. Next, the team is working to determine the efficiency with which genetically corrected iPS cells can increase muscle regeneration in DMD mice.
To ensure that stem cells grow to take on the proper architecture of a muscle, MDA-supported scientists led by Dr. Deok-Ho Kim are focused on developing materials that serve as scaffolds . Since muscle is a highly ordered tissue, with cells oriented in specific directions, these scaffolds may serve a critical purpose at the cellular scale to promote optimal growth of muscle in the most tissue-like patterns. In practice, the scaffolds are used for growing muscle from stem cells in the laboratory, which can then be transplanted into living organisms to replace damaged muscle. This work ultimately aims to generate a functional muscle patch capable of providing long-term muscle strength and regenerative capacity, and to improve symptoms in people with DMD.
Stem cell transplantation  remains a very promising approach for treating the muscle loss that occurs with DMD. Stem cells continue to be a major area of investigation for MDA-supported researchers. At this time, there are no therapeutic stem cell clinical trials being conducted in the U.S. in DMD. However, five trials (phases 1 and 2) are being conducted by researchers outside of the U.S., in the Middle East and Asia.
Activating satellite cells
In addition to stem cell transplantation, scientists are exploring the potential to use a more traditional drug approach to activate a patient’s own muscle stem cells. These muscle stem cells, called satellite cells  because of their position next to muscle cells, naturally exist to perform muscle repair. Preliminary work by several MDA-supported labs has shown that satellite cells become activated following inhibition of enzymes called histone deacetylases (HDACs). In a mouse model of DMD, HDAC inhibition induces muscle growth, decreases inflammation and reduces fibrosis. Building off of this preclinical work, researchers at a company called Italfarmaco are developing an HDAC inhibitor called Givinostat. This potential therapy is currently being tested in a phase 2 clinical trial in Italy.
MDA also has provided funding to support development of a protein known as WNT7a , which has been demonstrated to drive an expansion of the satellite stem cell population and facilitate muscle regeneration, resulting in significant functional improvement in preclinical models of muscular dystrophy. Based on these findings, a company called Fate Therapeutics is developing a drug-like compound base on WNT7a. This program is currently in preclinical development.
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Fortifying DMD muscle
DMD muscle is more susceptible to damage because it is missing dystrophin, a protein that sits at the muscle cell membrane and is critical for maintaining the muscle’s structural integrity. Thus, MDA supported scientists have devised a number of potential therapies that they hope will make DMD muscle more resistant to damage.
One potential strategy is to compensate for the lack of dystrophin with a similar muscle protein, such as utrophin. Utrophin is a naturally occurring structural protein that closely resembles dystrophin and performs a very similar function in the muscle. A key difference is that utrophin is produced during development or early stages of repair of muscle, and then is turned off and replaced by dystrophin (except for the area around where the nerve meets the muscle, where utrophin continues to be present in adult tissue). But scientists believe that if utrophin production were turned back on, it may be able to compensate for the absence of dystrophin.
MDA-supported scientists have identified a potential therapy that promotes production of utrophin protein in mice. This therapy, SMT C1100 , increases strength and fatigue resistance in a mouse model of DMD. SMT C1100 is being developed by Summit Therapeutics and has completed phase 1 safety testing in DMD boys. Summit is planning additional clinical testing to determine the effectiveness of SMT C1100 in DMD. Summit also is developing a second generation utrophin upregulator therapy called SMT022357, which is currently in preclinical development.
Another potential strategy to protect muscles from damage is to fortify DMD muscles using another naturally occurring structural protein called biglycan. Scientists reported in 2011 that systemically injecting the human form of 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, importantly, recruited utrophin to the muscle-fiber membrane. MDA has supported research by a company called Tivorsan  that has developed an engineered version of biglycan called TVN-102  that could be injected into patients. Tivorsan currently is preparing to take TVN-102 into early-stage clinical testing.
A third strategy to fortify DMD muscle is to introduce a different naturally occurring structural protein called Laminin 111. MDA has supported foundational research for this approach , where introduction of Laminin 111 was shown to improve exercise capacity and reduce muscle damage in a mouse model of DMD. Based on this work, a company called Prothelia Inc., in partnership with Alexion Pharmaceuticals, has developed an engineered version of laminin 111 called PRT-01. This potential therapy is currently in preclinical development for DMD as well as other dystrophies.
Researchers also are exploring whether muscle integrity could be strengthened by introduction of an enzyme called beta1, 4-N- acetylgalactosamine galactosyltransferase (GALGT2) using gene therapy. GALGT2 is involved in adding sugar molecules to a protein called alpha-dystroglycan, which is part of a cluster of proteins located at the muscle-fiber membrane. This cluster is abnormal in DMD muscle and previous work by MDA-supported scientists  has shown that raising GALGT2 levels in mice can help to compensate for the loss of dystrophin and protect muscle from damage. Since these findings were reported, GALGT2 gene therapy has been effectively delivered to calf muscles in macaque monkeys. Now, researchers at Nationwide Children’s Hospital aim to begin a phase 1 clinical study for GALGT2 gene therapy (rAAVrh74.MCK.GALGT2) for DMD in 2015.
In addition to identifying proteins such as utrophin, biglycan, laminin 111 and GALGT2 that may fortify against the loss of dystrophin, scientists are exploring other methods for protecting muscles from damage. For example, MDA-supported scientists have identified a compound called Carmaseal-MD  (Polaxamer 188 NF), which acts as a membrane sealant in a mouse model of DMD. In mice, this compound acts by filling the rips in the membrane  that result from damage. The company that is developing Carmaseal-MD, Phrixus Pharmaceuticals, hopes to begin clinical testing in people with DMD in 2016.
Suppressing the damage response
The repeated bouts of damage that occur in DMD muscle have been shown to eventually induce death (necrosis) of the muscle cells. Scientists believe that therapies which block the signals that contribute to cell death may one day be used to slow muscle degeneration and, in turn, loss of function.
Researchers have reported that an enzyme called hematopoietic prostaglandin D2 synthase (HPGDS) may contribute to the necrosis of muscle cells in DMD. To prevent muscle cell death, an inhibitor of this HPGDS, TAS-205, is being developed by Taiho Pharmaceuticals. This compound was shown to reduce necrosis and improve running in a mouse model of DMD. TAS-205 is now in early-stage (phase 1) clinical testing in Japan.
Scientists also have identified regulation of calcium in muscle as a potential strategy for therapeutic intervention. This approach is based on the fact that accumulation of calcium inside the cell, which is thought to happen in DMD, causes degradation of muscle proteins and triggers cell death. There is evidence that calcium does in fact play an important role in disease progression in DMD muscle, so several groups are investigating ways to ramp down accumulation of calcium in DMD muscle cells.
For example, an MDA-supported company called ARMGO has identified a compound called ARM210  that restores the appropriate balance of calcium within muscle cells by correcting the activity of a type of channel called the ryanodine receptor calcium channel complex (RyR). RyR functions to keep calcium safely sequestered away inside the cell until it is needed, but in DMD this channel has been shown to be leaky. But in a mouse model of DMD, ARM210 corrects the calcium leak occurring through the RyR and improves daily activity, strength, muscle force, and muscle damage. ARMGO is continuing preclinical validation of ARM210 and aims to begin clinical testing soon.
A second strategy to correct calcium accumulation in the cell is being developed by Akashi Therapeutics. The compound, called AT-300 (formerly GsMTx4), inhibits one of the channels that allows calcium to enter the muscle cell from the outside, called a stretch-activated calcium channel. AT-300 is based on a natural tarantula venom peptide, and acts to block calcium entry into muscle cells when they are being stretched. This compound is currently in preclinical development, but Akashi plans to bring it into clinical testing in the near future.
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During healthy muscle repair, inflammatory responses are activated and are known to aid in the cleanup and restoration of damaged muscle. In DMD, however, these inflammatory responses are chronically activated and therefore become detrimental to the repair process. MDA-supported scientists therefore are working to understand and interfere 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, to prevent scoliosis and to prolong the time that people with DMD can walk. 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.
MDA has invested heavily in researchers who are working on developing new anti-inflammatory therapies that have fewer or less severe side effects than the corticosteroids currently in use. Many of these potential therapies are being evaluated in clinical trials. These include VBP-15 , HT-100 , CAT-1004 , and deflazacort . VBP-15, made by ReveraGen BioPharma, is currently undergoing phase 1 safety study in healthy volunteers. HT-100, made by Akashi Therapeutics, is undergoing a phase 1-2 clinical study in DMD boys to determine whether it is both safe and effective. CAT-1004, made by Catabasis, will soon undergo testing in a phase 1 clinical study to determine its safety. Deflazacort, which is made by Marathon Pharmaceuticals and is a derivative of prednisolone, recently has begun a phase 1 clinical study in DMD boys in the U.S . Deflazacort already has been approved and available for several years in Europe and Canada.
One of the most advanced anti-inflammatory therapies, called Idebenone (Raxone/Catena), is being developed by Santhera Pharmaceuticals. In clinical trials, Idebenone had a positive impact on a measurement of respiratory function  (Peak Expiratory Flow, or PEF) in non-ambulatory DMD patients who were not taking steroids. Santhera has announced that it plans to apply for approval from the FDA for Idebenone in the near future.
Additionally, there are earlier-stage development efforts, such as IMO-8400 that are being developed by Idera Pharmaceuticals. IMO-8400 employs a unique strategy: inhibiting Toll-like Receptors (TLRs), proteins that are inappropriately upregulated in a mouse model of DMD. Idera is currently preparing to take IMO-8400 into phase 1 clinical trials with a goal of developing this drug for DMD.
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As muscles degenerate in a person with DMD, the muscle fibers are replaced by fat and connective tissue in a process called fibrosis. Fibrosis is similar to scarring, and the presence of fibrotic tissue in muscle impedes proper function and repair. In fact, scientists have observed that the extent of fibrosis in DMD muscle tracks with diminished function. Thus, MDA-supported researchers are investigating whether muscle function might be protected by medications, termed anti-fibrotics, that reduce this fibrosis. In addition, scientists hope that reducing fibrosis also may help increase the efficacy of other potential therapies. MDA has invested almost $4 million into investigating the potential of such therapies.
The most advanced drug in this class is currently being tested in a phase 2 trial — Akashi Therapeutics’ HT-100 . HT-100 is a delayed-release formulation of halofuginone, a compound that has been studied for years for its effects on autoimmune and fibrotic diseases. Halofuginone exerts its effects by inhibiting the formation of collagen 1, a major component of fibrotic tissue. MDA has strongly supported preclinical and clinical work with this compound that continues to show promise .
A second approach to reducing fibrosis is to introduce a peptide called angiotensin 1-7. In a mouse model of DMD, angiotensin 1-7 has been shown to reduce the formation of fibrotic tissue in muscle and also suppress some of the signals that have been implicated in the growth of fibrotic tissue. A company called Tarix Orphan LLC. is developing a therapy based on angiotensin 1-7, called TXA127. This therapy will undergo phase 2 clinical testing in 2016.
A third approach is to target connective tissue growth factor (CTGF), a common mediator of fibrotic disease. MDA has supported foundational work demonstrating a benefit of inhibiting CTGF in a mouse model of DMD. This work showed that CTGF reduces the ability of damaged muscle cells to repair themselves and promotes muscle fibrosis, and that inhibiting CTGF reduces muscle fibrosis and improves muscle function. Based on this preclinical work, a company called FibroGen is now developing a CTGF inhibitor, called FG-3019. FibroGen has recently received clearance from the FDA to begin phase 2 clinical testing of FG-3019 in DMD. In addition, FG-3019 also has been tested in phase 2 clinical studies for idiopathic pulmonary fibrosis, where it was shown to reverse fibrosis in a significant number of patients.
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People with DMD experience inadequate blood flow to their muscles while exercising, which may contribute to fatigue and reduced performance. Thus, scientists hope that drugs that restore proper blood flow to muscles may benefit muscle strength and function.
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 and pulmonary arterial hypertension.
On the basis of these and other findings, researchers have started investigating the possibility that phosphodiesterase inhibitors can improve muscle function in people with DMD or BMD.
In 2010, an MDA-supported trial testing the effects of tadalafil  on blood flow to muscles began in men with BMD. This study demonstrated that tadalafil could restore normal blood flow regulation after a single dose. Further study is ongoing to determine whether this effect will lead to improved muscle function in BMD.
A later study conducted in DMD found that treatment with either sildenafil or tadalafil restores blood flow to muscles during exercise or rest in DMD patients. Additional clinical studies are planned to determine whether this increased blood flow will translate to increased muscle function in DMD.
Of note, some research has focused on the effects of phosphodiesterase inhibitors on heart function in DMD and BMD. Unfortunately, a trial with sildenafil showed that it was unlikely to help heart function in these patient groups. A second study with sildenafil, which had enrolled a small number of participants, was in fact terminated due to concerns about the potential for negative impact on cardiac function in adults with Duchenne and Becker muscular dystrophy. Due to the small study size, questions remain about whether sildenafil is in fact unsafe for the BMD heart.
Nitric Oxide Donors
Scientists also are exploring the effect of modifying blood flow in DMD and BMD muscle with nitric oxide. Nitric oxide is the product of an enzyme called nNOS (which is absent in DMD and BMD muscle) and works in a similar manner to the phosphodiesterase inhibitors described above. Naproxinod is a potential therapy in preclinical development by a French pharmaceutical company called NicOx. Naproxinod is a version of naproxen (Aleve) that has been modified to release nitric oxide into the body. This therapy has been tested clinically for arthritis and other indications, and has demonstrated promising effects in a mouse model of DMD. The hope is that this therapy could increase blood flow to muscles and reduce inflammation, both of which may help to improve the function of DMD muscle.
Scientists in Italy are developing a combination therapy for DMD, using ibuprofen (a nonsteroidal anti-inflammatory drug) and isosorbide dinitrate (a nitric oxide donor). This combination therapy has undergone two clinical trials (named Isofen 1 and 2) to determine its safety and to establish the most effective dose of each drug. Additional clinical trials are planned to determine whether this combination has a beneficial effect in people with DMD.
Finally, researchers from Cedars-Sinai Medical Center currently are studying the effects of sodium nitrate, a nitric oxide donor, in people with BMD in two separate clinical trials. The first trial is a phase 2-3 study to determine whether sodium nitrate improves blood flow to muscle, as the phosphodiesterase inhibitors have been shown to do. The second is a phase 1 clinical study to determine whether there is a functional benefit to muscle that results from treatment with sodium nitrate.
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DMD heart muscle, like skeletal muscle, is more susceptible to damage because it is missing dystrophin, an important structural component of the cell membrane. As a result, some patients may develop cardiomyopathy or heart damage that weakens the heart’s ability to contract (pump). More information about cardiomyopathy in DMD can be found here and here.
Understanding and specifically treating dystrophin-deficient cardiomyopathy is a priority for MDA. The MDA DMD Clinical Research Network has made studying the natural history and treatment of this condition as 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.
To address DMD-associated cardiomyopathy, researchers are aggressively pursuing a number of strategies to sustain or improve heart function. They're testing already existing medications for their possible benefits in the DMD affected heart, and also conducting research to find new approaches to specifically treat the dystrophin-deficient heart.
Since a number of cardiomyopathy drugs have been developed over the years to treat heart failure in older patients, doctors already have some tools at their disposal for treating the DMD heart. These therapies center on ways of reducing the burden on the pumping heart. To that end, doctors may prescribe angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) that make blood vessels open up wide and thereby reduce the resistance to the heart’s pumping action. Doctors may also prescribe diuretics to remove extra water from the blood, so that there is less volume for the heart to pump. Finally, doctors may prescribe beta-blockers to slow the heart rate, giving the DMD heart sufficient time to empty and refill with each beat so that it can pump blood more efficiently.
Researchers are continuing to study existing drugs to determine the best regimen to preserve heart function in DMD. Currently, there are several clinical studies aimed at determining the best combination and dose to prevent decline of heart function. These include studies of the relative efficacy of the aldosterone receptor antagonist, spironolactone and eplerinone, which are diurectics. This is a phase 3 clinical study led by Dr. Subha Raman at Ohio State University. Prior work by this group demonstrated that treatment with eplerinone (along with ACE inhibitors or ARBs) slowed the decline of cardiac function in boys with DMD over the course of one year. Additional studies investigating the optimal drug regimen for slowing cardiac decline in DMD include a phase 4 study in Italy comparing the effects of carvedilol (a beta blocker) with Ramipril (an ACE inhibitor), and a phase 3 study in France examining the effects of nebivolol (a beta blocker).
One promising and completely new therapy in development specifically for DMD is called CAP-1002 and is being developed by Capricor Therapeutics. CAP-1002 is a therapy based on cardiac stem cells (jump to stem cell transplantation) derived from donor heart tissue. Researchers aim to transplant these therapeutic stem cells into people with DMD with the hope that they will promote repair of the heart. Studies with CAP-1002 in a mouse model of DMD have demonstrated positive effects on the heart, and the company has since initiated a phase 1-2 clinical study to test the safety and effectiveness of CAP-1002 in boys and men with DMD.
Another new therapy, called PB1046, is in development by PhaseBio Pharmaceuticals. PB1046 is an engineered version of Vasoactive Intestinal Peptide (VIP), a neuropeptide which has been shown to be ionotropic (increases contraction of the heart) and lusitropic (speeds relaxation of the heart). VIP has also been shown to prevent fibrosis and inflammation in cardiac and skeletal muscle. PhaseBio has reported that their engineered version of VIP, PB1046, slowed cardiac functional deterioration in two mouse models of DMD and showed positive safety data in a clinical trial with volunteers who had essential hypertension. PhaseBio plans to begin phase 1 clinical testing to determine the safety of PB1046 in people with DMD in 2016.
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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 to evaluate biomedical or health-related outcomes, including experimental medications or therapies. 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.)
Clinical trials are conducted in a series of successive steps, called phases. Each phase is designed to answer a separate research question.
*Note: Some clinical trials are not assigned a phase by the U.S. Food and Drug Administration (FDA). These include trials that test devices or behavioral interventions.
|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.