MDA leads the search for treatments and therapies for spinal muscular atrophy (SMA). The Association also provides comprehensive supports and expert clinical care for those living with SMA.
In this section, you’ll find up-to-date information about spinal muscular atrophy, 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 SMA, 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 SMA 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 spinal muscular atrophy. 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 SMA community. We urge you to contact your local MDA office  to learn more.
An SMA 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 spinal muscular atrophy.
Never forget that MDA is here to help.
|The muscles closer to the center of the body (proximal muscles) are usually more affected in spinal muscular atrophy than are the muscles farther from the center (distal muscles).|
Spinal muscular atrophy (SMA) is a genetic disease affecting the part of the nervous system that controls voluntary muscle movement.
Most of the nerve cells that control muscles are located in the spinal cord, which accounts for the word spinal in the name of the disease. SMA is muscular because its primary effect is on muscles, which don’t receive signals from these nerve cells. Atrophy is the medical term for getting smaller, which is what generally happens to muscles when they’re not active.
SMA involves the loss of nerve cells called motor neurons in the spinal cord and is classified as a motor neuron disease.
In the most common form of SMA (chromosome 5 SMA, or SMN-related SMA), there is wide variability in age of onset, symptoms and rate of progression. In order to account for these differences, the chromosome 5 SMA often is classified into types 1 through 4.
The age at which SMA symptoms begin roughly correlates with the degree to which motor function is affected: The earlier the age of onset, the greater the impact on motor function. Children who display symptoms at birth or in infancy typically have the lowest level of functioning (type 1). SMA onset in children (types 2 and 3), teens or adults (type 4) generally correlates with increasingly higher levels of motor function.
For more, see Forms of SMA .
What causes SMA?
Chromosome 5 SMA is caused by a deficiency of a motor neuron protein called SMN, for “survival of motor neuron.” This protein, as its name implies, seems to be necessary for normal motor neuron function. Its deficiency is caused by genetic flaws (mutations) on chromosome 5 in a gene called SMN1. Neighboring SMN2 genes can in part compensate for nonfunctional SMN1 genes.
Other rare forms of SMA (non-chromosome 5) are caused by mutations in genes besides SMN.
What are the symptoms of SMA?
SMA symptoms cover a broad spectrum ranging from mild to severe.
The primary symptom of chromosome 5-related (SMN-related) SMA is weakness of the voluntary muscles. The muscles most affected are those closest to the center of the body, such as those of the shoulders, hips, thighs and upper back. Special complications occur if the muscles used for breathing and swallowing are affected, resulting in abnormalities in these functions. If the muscles of the back weaken, spinal curvatures can develop.
There's a great deal of variation in the age of onset and level of motor function achieved in chromosome 5-related SMA. These are roughly correlated with how much functional SMN protein is present in the motor neurons, which in turn is correlated with how many SMN2 genes a person has.
Sensory, mental and emotional functioning are entirely normal in chromosome-5 SMA.
Some forms of SMA are not linked to chromosome 5 or SMN deficiency. These forms vary greatly in severity and in the muscles most affected. While most forms, like the chromosome 5-related form, affect mostly the proximal muscles, other forms exist that affect mostly the distal muscles (those farther away from the body’s center) — at least in the beginning.
For more, see Signs and Symptoms .
What is the progression of SMA?
In chromosome 5-related SMA, the later the symptoms begin and the more SMN protein there is, the milder the course of the disease is likely to be. While in the past, infants with SMA typically did not survive more than two years, today most doctors now consider SMN-related SMA to be a continuum and prefer not to make rigid predictions about life expectancy or weakness based strictly on age of onset.
What is the status of research on SMA?
Research has focused on strategies to increase the body's production of SMN protein, lacking in the chromosome 5-related forms of the disease. Approaches in this and other forms of SMA include methods to help motor neurons survive in adverse circumstances.
Spinal muscular atrophy types 1 through 4 all result from a single known cause — a deficiency of a protein called SMN, for "survival of motor neuron."
Deficiency of SMN protein occurs when a mutation (flaw) is present in both copies of the SMN1 gene — one on each chromosome 5. Normally, most of the protein made from SMN1 genes is full-length and functional, but when mutations occur, little or no full-length, functional SMN protein is produced.
This loss can be partially offset by the presence of neighboring SMN2 genes, which are similar in structure to SMN1 genes. Most of the protein made from SMN2 genes is short and not functional, but some is full-length and functional. The number of SMN2 genes varies from person to person.
In chromosome 5-related SMA, the more copies of the SMN2 gene that a person has, the more functional SMN protein is available, the later the onset of disease symptoms, and the milder the disease course is likely to be.
When SMA symptoms are present at birth or by the age of 6 months, the disease is called type 1 SMA (also called infantile onset or Werdnig-Hoffmann disease). Babies typically have generalized muscle weakness, a weak cry and breathing distress. They often have difficulty swallowing and sucking, and don't reach the developmental milestone of being able to sit up unassisted. Typically these babies have two copies of the SMN2 gene, one on each chromosome 5. Over half of all new SMA cases are SMA type 1.
When SMA has its onset between the ages of 7 and 18 months and before the child can stand or walk independently, it is called type 2 or intermediate SMA. Children with type 2 SMA generally have at least three SMN2 genes.
Late-onset SMA (also known as types 3 and 4 SMA, mild SMA, adult-onset SMA and Kugelberg-Welander disease) results in variable levels of weakness.
Type 3 SMA has its onset after 18 months, and children can stand and walk independently, although they may require aids. Type 4 SMA has its onset in adulthood, and people are able to walk during their adult years. People with types 3 or 4 SMA generally have between four and eight SMN2 genes, from which a fair amount of full-length SMN protein can be produced.
For more about the differences among types 1 through 4 SMA, see Signs and Symptoms .
Other forms of SMA are not related to a deficiency of SMN protein, arising instead from defects in different genes on different chromosomes. These forms vary greatly in severity and in the muscles most affected.
Spinal Muscular Atrophy with Respiratory Distress (SMARD) is a rare form of SMA caused by defects in the IGHMBP2 gene. Infants with SMARD present with severe respiratory distress as well as muscle weakness.
Another rare form of SMA, distal SMA, more severely affects the hand and feet muscles. Distal SMA can be inherited in a recessive fashion similar to SMA types 1-4, in which both parents contribute a faulty copy of the SMN1 gene. Alternatively, distal SMA can be inherited from just one parent (dominant inheritance). Distal SMA can also be X-linked, meaning the gene defect is on the X chromosome. Like most X-linked diseases, this form of distal SMA is much more likely to occur in males than in females.
A number of genetic causes have been identified for distal SMA, which is associated with varying symptoms and severity. Some of the genes shown to cause various forms of distal SMA include UBA1, DYNC1H1, TRPV4, PLEKHG5, GARS, and FBXO38. Some of these forms of SMA overlap with another disease called Charcot-Marie-Tooth Disease (CMT) . Diagnosis typically depends on the degree of motor versus sensory symptoms observed in the patient.
A mutation in an X-chromosome gene called UBE1 causes X-linked SMA. This form resembles type 1 SMA (see above) in its very early age of onset and severity of symptoms. Joints as well as muscles may be affected in X-linked SMA. Like most X-linked diseases, it's much more likely to occur in males than in females.
Flaws in the cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) gene on chromosome 14 lead to another rare form of SMA, called SMA-LED. This form affects primarily the muscles in the legs.
While all known forms of SMA are apparently genetic, they result from defects in different genes, and have different inheritance patterns  and implications for family planning.
If you or your child has been told the diagnosis is SMA but it’s not the chromosome 5-related type, talk with your doctor and perhaps a genetic counselor to find out more about the genetics and prognosis for the particular SMA involved.
In SMA types 1 through 4, symptoms vary on a continuum from severe to mild, based on how much SMN protein there is in the nerve cells called motor neurons. (SMN stands for survival of motor neuron.) The more SMN protein there is, the later in life symptoms begin and the milder the course of the disease is likely to be.
Children who have noticeable SMA symptoms at or shortly after birth usually are very weak, have difficulty breathing, sucking and swallowing, and never reach the developmental milestone of being able to sit on their own (type 1 SMA or Werdnig-Hoffmann disease). In the past, children with type 1 SMA usually didn't survive more than two years, but today this is not always the case. With technology such as mechanical ventilation and feeding tubes to assist with breathing and nutrition, children with type 1 SMA can survive for a number of years.
When SMA symptoms begin in babies at approximately 7 to 18 months of age, who learn to sit unassisted but not to stand or walk independently, the disease usually is called type 2 SMA, or intermediate SMA. Although respiratory complications are a constant threat, children with type 2 SMA usually live to young adulthood and many live longer.
When muscle weakness begins in older children and teens, who learn to stand and walk but lose the ability later in life, the disease may be labeled type 3 SMA (also known as mild SMA and Kugelberg-Welander disease). Although some with type 3 stop walking in adolescence, others walk well into their adult years. SMA that comes on in late teens or adulthood is called type 4, or adult-onset SMA. Life span is generally normal in these two types.
In SMA types 1 through 4, the muscles closer to the center of the body (proximal muscles) usually are more affected, or at least affected much sooner, than the muscles farther away from the center. For example, the muscles of the thighs are weaker than the muscles of the lower legs and feet.
|Scoliosis (spinal curvature) is a common problem in SMA and should be corrected.|
Legs tend to weaken before arms. Hands may weaken eventually, but they usually stay strongest the longest, and, even if they do weaken, they usually remain strong enough for typing on a computer keyboard and other basic functions of modern life.
The most serious danger in SMA comes from the weakness of muscles necessary for breathing. Careful attention to respiratory function is needed throughout life, with prompt attention to infections.
Your doctor can help you with details of maintaining respiratory health, including clearance of secretions and perhaps assisted ventilation  (not necessarily around the clock).
Another medical complication in SMA is spinal curvature, usually a side-to-side type of curvature called scoliosis. Scoliosis occurs because of weakness of the muscles that normally support the spine, which is a flexible column.
Scoliosis can be very uncomfortable, interfere with position and mobility and damage a child’s (or adult’s) body image. Some studies have shown that spinal curvatures, if they’re severe, can interfere with breathing.
Many children with SMA start to show a scoliotic curve early in life, which is often treated with a brace until the right time for surgery is reached.
Surgeons generally like to wait until growth is complete or nearly so before surgically straightening and fusing the spine . They also take into account the child’s pulmonary function and how fast the curve is likely to progress.
Some forms of SMA are not linked to chromosome 5 or SMN deficiency. These forms vary greatly in severity and in the muscles most affected. While most forms, like the chromosome 5-related form, affect mostly the proximal muscles, other forms exist that affect mostly the distal muscles, those farther away from the body’s center, at least at the beginning.
The first steps in diagnosis of a neuromuscular disease are usually an in-office physical examination and family history, with some simple tests to distinguish spinal muscular atrophy (SMA) from similar conditions (such as muscular dystrophy).
The doctor may order a blood test for an enzyme called creatine kinase (CK) , an enzyme that leaks out of muscles that are deteriorating. This is a nonspecific test because CK levels are elevated in many neuromuscular diseases, but it’s often useful anyway. High blood CK levels aren’t harmful in and of themselves, but they do indicate that muscle damage has occurred.
The doctor probably will recommend genetic testing if SMA is suspected, because this is the least invasive and most accurate way to diagnose chromosome 5-related SMA (types 1-4). Genetic testing requires only a blood sample. However, it has implications for the whole family that must be considered (see Causes/Inheritance ).
Genetic tests are available for chromosome 5-related SMA and for some of the other forms of SMA. See Athena Diagnostics , a Massachusetts company that offers genetic testing for many neuromuscular diseases, including SMA; and Gene Tests , a website supported by the National Center for Biotechnology Information and sponsored by the University of Washington-Seattle, that lists available genetic tests.
Reliability and specificity of genetic tests are improving, and the number of tests available is expanding rapidly as knowledge and technology improve. For more on getting a definitive genetic diagnosis, see The Genie's Out of the Bottle: Genetic testing in the 21st century . Your MDA clinic team can guide you toward the right type of genetic testing for your situation.
In rare cases, doctors may order a muscle biopsy , which involves taking a small sample of muscle tissue, usually from the thigh, and looking at it under a microscope.
Other tests sometimes used to diagnose SMA include one that measures nerve conduction velocity  — the speed with which signals travel along nerves — and one that measures the electrical activity in muscle, called an electromyogram, or EMG. Nerve conduction velocity tests involve sensations that feel like mild electric shocks, and EMGs require that short needles be inserted in the muscles.
|Muscle-controlling nerve cells (motor neurons) are located mostly in the spinal cord. Long, wirelike projections connect the motor neurons to muscles in the limbs and trunk. Normally, signals from the neurons to the muscles cause muscles to contract. In SMA, motor neurons are lost, and muscles can’t function.|
SMA is characterized by the loss of nerve cells in the spinal cord called motor neurons. It is classified as a motor neuron disease.
The most common form of SMA (types 1-4) is caused by a defect (mutation) in the SMN1 gene on chromosome 5. (People have two SMN1 genes — one on each chromosome 5.)
A mutation in the SMN1 gene leads to a deficiency of a motor neuron protein called SMN, for survival of motor neuron. As its name implies, this protein seems to be necessary for normal motor neuron function.
More rarely, a mutation in an X-chromosome gene called UBE1 causes X-linked SMA. The UBE1 gene carries instructions for ubiquitin-activating enzyme 1, which normally helps attach a molecular tag to proteins to mark them for destruction by a cell.
Flaws in the cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) gene on chromosome 14 have been found to lead to another rare form of SMA, called SMA-LED.
Normally, SMN1 genes produce full-length and fully functional SMN protein. But when the SMN1 gene has mutations, as in the chromosome 5-related form of SMA, insufficient levels of SMN protein are produced.
There is a neighboring gene on chromosome 5, called SMN2, which also produces SMN protein. Most of the protein made from instructions carried by SMN2 genes is not functional, but a small percentage is.
People can have multiple copies of the SMN2 gene. In the chromosome 5 form of SMA, the more SMN2 genes a person has, the more functional SMN protein is available. And the milder the disease course is likely to be.
Genetic testing can tell how many SMN2 genes a person has and roughly predict the course of SMA that is likely to result.
SMA severity also may depend on disease modifiers, which don't cause disease but can affect (modify) onset and severity by influencing various biological pathways. Levels of both the plastin 3 protein  and the ZPR1 protein  have been identified as modifiers of SMN-related SMA and could become therapeutic targets. In addition, testing for these protein levels could help predict disease severity, and insight into the activities of these proteins could shed new light on disease processes.
|Genetic information moves from its storage form as DNA to a set of instructions known as RNA, from which protein molecules are made. Most of the RNA instructions from the SMN1 gene tell the cell to make full-length SMN protein. Most of the instructions from the SMN2 gene tell the cell to make short SMN protein.|
Chromosome 5 SMA (types 1 through 4) follows an inheritance pattern known as autosomal recessive, which often takes families by surprise. (The autosomes are the numbered chromosomes — that is, all the chromosomes except the X and the Y, which determine gender.)
Diseases that are recessive require two gene flaws — usually one from each parent, but occasionally one from one parent and one that occurs as a fetus is being formed.
People who have only one gene flaw for a recessive disease are said to be carriers and usually show no symptoms. Often, a family has no idea that some members are carriers until a child is born with a recessive disorder.
If both parents are carriers of the chromosome 5 gene flaw, the risk of each pregnancy producing a child with the disease is 25 percent. This risk doesn’t change no matter how many children a couple has. The "dice are rolled" with each new conception.
Genetic testing for chromosome 5 SMA is available for those suspected of having the disease, including unborn babies, and for carriers of the disease.
Genetic testing is expanding and changing rapidly, but its implications can be complex. It’s best to talk with a genetic counselor before embarking on testing. (A genetic counseling referral can be obtained through your MDA clinic .)
X-linked SMA is inherited in an X-linked manner (via the X chromosome). Females have two X chromosomes, and those with a gene flaw on one X chromosome are usually considered carriers of an X-linked disease. Males, however, have no second X to protect them from the full effects of a gene flaw on the X chromosome and show the full effects of such a flaw.
SMA caused by mutations in the DYNC1H1 gene on chromosome 14 is dominantly inherited, meaning that only one DYNC1H1 gene mutation, inherited from one parent, is sufficient to cause the disease.
To read more about the genetics of SMA and genetic testing for this disease, also see:
This section addresses the medical management of:
This section also answers the following questions:
For more medical guidance, see the Spinal Muscular Atrophy Care Guidelines .
|Noninvasive ventilation can be delivered through a mask or mouthpiece. Photo courtesy of Respironics.|
|A device that assists with coughing can help clear respiratory secretions. Photo courtesy of Respironics.|
In several forms of SMA, respiratory muscle weakness is a significant problem. It’s the most common cause of death in types 1 and type 2 chromosome 5 (SMN-related) SMA.
When the respiratory muscles weaken, air doesn’t move into and out of the lungs very well, with subsequent adverse effects on general health. Signs of weakening respiratory muscles are headaches, difficulty sleeping at night, excess sleepiness during the day, poor concentration, chest infections and, eventually, heart damage and respiratory failure.
Often, in infantile-onset SMA, the muscles between the baby's ribs are very weak, while the diaphragm muscle stays fairly strong. This leads to children who appear to be breathing by moving their bellies rather than their chests and to a pear-shaped body in these infants.
In recent years, the availability of portable, effective ventilation devices has created more options for newborns with SMA, and some have surprised their families and physicians by living many years.
Assisted ventilation also can help children and adults with different forms of SMA. Many physicians advise starting out with noninvasive ventilation , which generally means that air (usually room air, not enriched with oxygen) is delivered under pressure through a mask or mouthpiece.
This kind of system comes in many forms and can be used as many hours of the day and/or night as necessary. It can easily be removed for eating, drinking and talking.
When noninvasive ventilation isn’t sufficient, ventilation assistance can delivered through a tracheostomy  — a surgical hole in the trachea, or windpipe. Air under pressure is then delivered through a tube in the tracheostomy site. After a period of adjustment, it’s usually possible for people to eat, drink and talk with a tracheostomy tube.
Other necessary aspects of respiratory care in SMA include clearance of respiratory secretions, sometimes also achieved with a mechanical device, and prevention of infection as far as possible.
An insufflator-exsufflator is one type of device that can assist with clearing respiratory secretions from the airway. The device applies positive pressure to the airway and then rapidly reverses to negative pressure, mimicking a natural cough. The CoughAssist , made by Philips Respironics, is an example of this type of device.
Another type of airway clearance aid is a high-frequency chest wall oscillation device. This device is a vest that rapidly inflates and deflates, vibrating the chest and creating "mini-coughs" that dislodge mucus from small airways, moving it toward larger airways from which it can be more easily coughed out. The Vest Airway Clearance System , made by Hill-Rom, is an example.
To prevent respiratory infections, almost everyone with SMA should get a flu shot every year. Other precautions include staying away from crowds and getting adequate rest and nutrition.
The MDA clinic  team can advise you about respiratory care, flu shots and related matters.
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Swallowing problems occur when the muscles of the mouth and throat are weak.
Babies with infantile-onset SMA usually have trouble swallowing and sucking. Sucking weakness can lead to dehydration and poor nutrition, while swallowing weakness can lead to obstruction of the airway and respiratory infections from inhaled food or liquids (aspiration).
Babies with severe swallowing and sucking weakness can be fed by alternative methods, such as a feeding tube, often called a gastrostomy tube or g-tube. A feeding tube is a small, flexible tube, about the diameter of a pencil, that allows liquid nutrition (homemade or commercially prepared) to enter the stomach directly, bypassing the mouth, throat and esophagus. Some feeding tube systems are constructed so that the tube can be detached from a "button" on the abdomen when it’s not in use.
Some g-tube users also can eat and drink by mouth, in addition to using the tube. If the main problem is weakness of the chewing muscles, making eating laborious and time-consuming, then it’s fine to eat by mouth for pleasure and extra nutrition, and use the g-tube for basic calories. By contrast, if the main reason for the tube is aspiration of food and liquid, then it’s probably not safe to eat and drink by mouth.
Speech-language pathologists (SLPs)  are educated in treating swallowing problems as well as those associated with speech.
Your MDA clinic  team can advise you about swallowing muscle weakness, including special ways of preparing food and the use of gastrostomy tubes.
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|This girl with type 2 SMA used a back brace as a toddler. At 9, she underwent surgery to correct a spinal curvature, and wore a temporary brace while recovering from surgery.|
Weakness of the muscles of the back that normally support the flexible, growing spine is a major problem in childhood-onset SMA. If it’s not corrected, the child may develop scoliosis — a side-to-side curvature of the spine — or kyphosis, a forward curvature of the spine, or both. Some may even end up with "pretzel" types of curvatures that make it impossible to sit or lie down with comfort.
Some physicians believe that severe spinal curvatures may compromise respiratory function in some cases, if the curved spine compresses a lung.
A back brace or corset that supports the child in a certain position is often prescribed to try to direct the spine as it’s growing. Braces don’t solve the problem, but they may slow the progression of a curve.
The permanent solution to spinal curvature is almost always spine-straightening surgery , which can be done if the child’s respiratory status is good enough to withstand the surgery.
The timing of back surgery is tricky. Doctors generally like to wait until maximum spinal growth has been achieved because that allows a simpler surgical technique to be used. On the other hand, if respiratory status is deteriorating, surgery often can’t wait until growth is complete. Here again, the MDA clinic  can help you decide.
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A child or adult with SMA who must undergo surgery (for example, to correct scoliosis) needs to take special precautions. The surgical team, particularly the anesthesiologist, must thoroughly understand SMA.
Sometimes, especially in the early stages of SMA, the muscle cells that aren’t receiving nerve signals develop certain abnormalities as they try to "reach out" to nerves. These abnormalities can lead to dangerous reactions to muscle-relaxing drugs  often used during surgery. Doctors can get around this problem, if they’re aware of it, by using different drugs.
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Many people wonder if a special diet will affect the course of SMA. While it’s certainly true that children and adults with SMA need good nutrition, so far, there’s little evidence to suggest that any particular type of diet is useful against SMA — and in fact some diets may be harmful.
For example, special formulas made up of broken-down protein components called amino acids — so-called "elemental diets" — actually may cause problems for children with SMA who have little muscle tissue. Some experts say blood levels of these amino acids can become too high if there isn’t enough muscle tissue to properly use them.
Children and adults with SMA run the risk of becoming overweight, probably because they can’t exercise effectively and are taking in too many calories for their level of activity. With the guidance of a physician or nutritionist, it should be possible to keep weight under control , which is important for health, appearance and the backs of caregivers who help with lifting and transferring.
Some children may do better with small, frequent feedings than with three large meals a day. In addition, some physicians recommend over-the-counter supplements, including creatine and/or coenzyme Q10, to meet nutritional needs.
Your MDA clinic  physician and other staff members at the clinic can help you with nutritional issues for yourself or your child.
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In SMA, most physicians advise that doing as much physical activity as is comfortable without going to extremes is a good idea, in order to maintain general physical and psychological health and well-being.
It’s important to protect joints from stiffness or injury, preserve range of motion (flexibility in the joints), maintain circulation and, especially for children, allow enough mobility for exploration of the environment.
Exercising in a warm pool (85 to 90 degrees) may be particularly beneficial. A person with SMA shouldn’t swim alone, and appropriate safety precautions should be provided.
|Adults with SMA are often able to drive with specialized hand controls.|
While some physical therapy experts believe over-exercising muscles is not a problem, others believe exercising to exhaustion can "burn out" remaining motor neurons before their time. More research is needed in this area; in the meantime, it seems sensible to exercise with discretion  and stop before reaching the point of exhaustion.
For more information, see Exercising with a Muscle Disease .
Physical therapy  and occupational therapy programs can help children and adults learn the best ways to maximize their muscle function and accomplish activities of daily living. A referral to a physical or occupational therapist can be obtained through your MDA clinic .
An array of assistive technology products can help even very young children explore the world despite having very weak muscles. Standers , walkers, various kinds of powered and manual wheeled vehicles, and braces (orthoses) can help with standing and moving around. Therapists also can help teachers and parents find the best physical solutions for the school environment.
Other useful technology can help with writing, painting, using a computer or telephone, and electronically controlling the environment (for example, temperature, lighting, television and so forth).
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The research picture has brightened considerably in the last decade for people with chromosome 5-related spinal muscular atrophy types 1 through 4, thanks to special genetic circumstances that provide researchers with unique opportunities for intervention.
Since 1995, scientists have known that a deficiency of functional SMN protein is the underlying cause of chromosome 5 SMA. (SMN stands for survival of motor neuron.)
Two nearly identical genes carry the genetic instructions for the SMN protein: SMN1 and SMN2. Proteins made from the SMN1 gene are full-length and functional, and appear to be necessary for the survival and proper function of the motor neurons. By contrast, proteins made using instructions from the SMN2 gene are shorter and tend to be less stable.
In SMA types 1 through 4, flaws (mutations) in each of the two copies of the SMN1 genes result in insufficient production of full-length, functional SMN protein.
Fortunately, a certain amount of full-length SMN protein can be made from the SMN2 gene. Many people have multiple copies of the SMN2 gene. These extra SMN2 genes can lessen the impact of a flaw in both SMN1 genes. In chromosome 5-related SMA, the more SMN2 genes a person has, the milder the course of SMA is likely to be.
Researchers are seeking to exploit this unique redundancy through development of various strategies that restore sufficient levels of the needed full-length SMN protein.
Since inception, MDA has contributed over $44 million dollars to SMA research.
Here is a look at some of the leading research strategies currently being tried in different forms of SMA. Additionally, please visit Grants at a Glance  to read about some of the specific projects currently funded by MDA.
One research strategy to treat chromosome 5-related SMA types 1 through 4 is based on transferring SMN1 genes into the body to raise the level of full-length SMN protein. In a 2010 U.S. experiment, very young mice with an SMA-like disease  received intravenous injections of genes containing instructions for the SMN protein, packaged inside modified type 9 adeno-associated viruses (AAV9 vehicles). The AAV9 vehicle reached its target — motor neurons in the spinal cord — and increased levels of SMN protein were subsequently found in the animals' brains, spinal cords and muscles. The mice showed dramatic improvement of motor function and brain-to-muscle signaling, and a significant increase in survival. (This same gene delivery method later was successfully used in a monkey, although the monkey didn't have an SMA-like disease. A similar method was used in a pig model of SMA as well, with promising results.)
Also in 2010, a British research group transferred SMN genes inside AAV9 delivery vehicles  intravenously into mice with an SMA-like disease, improving the life span in these mice.
Brian Kaspar at Nationwide Children's Hospital in Columbus, Ohio, discusses gene transfer in SMA  in a May 2010 podcast. Dr. Kaspar, together with the biotechnology company AveXis, is developing this gene therapy approach for use in SMA patients. A phase 1 clinical trial testing whether intravenous delivery of AAV9-SMN could help type 1 SMA patients is ongoing.
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Another strategy in development for SMA is using antisense oligonucleotides to cause more full-length SMN production from SMN2 genes. The SMN2 gene is similar in structure to the SMN1 gene. However, most of the protein made from the SMN2 gene is short and not functional. The antisense oligonucleotides alter how the SMN2 RNA is put together to increase the amount of full-length, functional SMN. In 2010, MDA-supported scientists announced that mice with an SMA-like condition  showed a "robust and long-lasting increase" in full-length SMN protein in their spinal cords and in the motor neurons themselves after experimental antisense treatment. A February 2012 podcast  features researcher Arthur Burghes discussing the antisense strategy.
Based off of laboratory research findings, ISIS Pharmaceuticals is developing an antisense oligonucleotide therapy called ISIS-SMNRx, which is currently in clinical trials. The antisense oligonucleotide has been administered in several trials to SMA patients including people with types 1, 2, and 3. Thus far, ISIS-SMNRx appears to be safe and well-tolerated and has shown encouraging results in some SMA patients in phase 2 trials. ISIS Pharmaceuticals is currently testing this drug in phase 3 clinical trials.
Genetic information moves from its storage form as DNA to a set of instructions known as RNA, from which protein molecules are made. Most of the RNA instructions from the SMN1 gene tell the cell to make full-length SMN protein. Most of the instructions from the SMN2 gene tell the cell to make short SMN protein.
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Several research strategies involve manipulating the genetic instructions provided by the SMN2 gene so that more full-length SMN protein can be made. The SMN2 gene is similar in structure to the SMN1 gene. However, most of the protein made from the SMN2 gene is short and not functional. This research approach uses small molecule drugs that target the SMN2 gene to change how the SMN2 RNA is put together, with the goal of increasing production of full-length, functional SMN or to increase the overall level of SMN through other means.
Groups of pharmaceutical companies are testing different drugs that act through this approach in SMA patients. Novartis is beginning a phase 2 trial in type 1 SMA patients to test their drug called LMI070. Additionally, Roche, together with PTC Therapeutics, initiated a phase 2 clinical trial to test their drug RG7800 in SMA patients. With MDA support, a company called Repligen has developed an experimental compound called RG3039 (also called quinazoline) , which is designed to interfere with an enzyme and thereby increase production of full-length SMN protein from the SMN2 gene. This drug is currently being tested in a phase 1 clinical trial in healthy volunteers.
Other companies developing drugs to increase levels of full-length SMN currently are in the preclinical development stage. Paratek Pharmaceuticals is working on a small molecule compound that is similar to an antibiotic called tetracycline. Additionally, the California Institute for Biomedical Research (CALIBR) is in the process of optimizing drugs that upregulate SMN levels through a different mechanism than RNA splicing.
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An X chromosome gene has been identified that, when mutated, causes X-linked SMA. The gene codes for the UBE1 protein, which is part of a cellular waste disposal system. Without functional UBE1 protein, this important waste disposal system probably malfunctions.
Scientists are now studying the UBE1 gene and protein  with an eye to identifying therapeutic targets in X-linked SMA.
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Motor neurons are a specialized type of nerve cell that dies in people with SMA. These motor neurons are the wires that connect the brain and spinal cord to the muscles, and their death leads to muscle weakness and paralysis in SMA. One approach researchers are pursuing for SMA focuses on protecting muscles from paralysis and increasing their strength. Although this approach does not fix the underlying genetic problem in SMA, drugs that enhance muscle function could likely be used in combination with other therapies that act on the SMN genes.
Cytokinetics is developing drugs that increase the ability of the muscle to contract. These drugs have shown early promise in patients with a similar motor neuron disease called amyotrophic lateral sclerosis (ALS) . Together with Astellas, Cytokinetics is developing a similar drug called CK-2127107 for SMA. This drug has been tested in a phase 1 clinical trial of healthy volunteers, where it proved to be safe and able to increase muscle force. Cytokinetics is planning to test CK-2127107 in a phase 2 clinical trial in SMA patients.
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Most evidence suggests that treatment of babies with type 1 SMA should be done as early in life as possible, and that it may be necessary to start screening for the disease in newborns to identify them early. Newborn screening is performed for many diseases and could be one means to identify and treat infants with SMA before they lose motor function. There are efforts underway to conduct pilot studies in certain areas to assess the feasibility of newborn screening for SMA. If a robust treatment for SMA becomes approved in the US, newborn screening for the disease may be pursued for all babies.
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Flaws in the cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) gene on chromosome 14 can lead to a rare form of SMA called SMA-LED, which predominantly affects muscles in the legs. The DYNC1H1 gene works as a "motor" to transport cellular components. Mutations in the DYNC1H1 gene result in disruptions to the motor's function. Much work is yet to be done on this newly discovered cause of SMA .
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Motor neurons are the nerve cell type that degenerates in SMA, leading to muscle weakness and paralysis. While some research is focused on strategies to increase SMN levels to help motor neurons, other scientists are focusing on broad neuroprotection. This research aims to prevent motor neurons from becoming dysfunctional and dying rather than altering the genetics of the SMN genes. Neuroprotective strategies could likely be used in combination with other drugs that address the underlying genetic problem in SMA.
In 2007, the French company Trophos identified a novel compound called olesoxime (TRO19622) that was able to protect motor neurons from death in a dish. Since then, olesoxime has been tested in SMA patients in clinical trials with encouraging results. A phase 2 trial conducted on types 2 and 3 SMA patients in Europe showed that olesoxime preserved motor function and seemed safe and well-tolerated. Trophos, which was acquired by Roche in 2015, has planned to file a New Drug Application (NDA) with the FDA in the US in order to move olesoxime forward.
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For many diseases, there are indicators in the body that change when a person has a disease or when the disease gets worse or better. These indicators are called “biomarkers” and can be found by testing the blood or urine, or by using other more sophisticated types of testing, such as nerve conduction tests commonly used to diagnose motor neuron disorders. One area of active research within the SMA field is to identify biomarkers which could be used to tell how SMA patients are progressing and whether they are responding to a potential treatment. Since motor function tests can be variable and difficult to conduct, especially in young infants, identification of biomarkers would be useful in the efforts to find treatments for SMA.
SMA biomarkers are currently being evaluated in the NIH NeuroNEXT clinical trial, titled “SMA Biomarkers in the Immediate Postnatal Period of Development.” In this trial, infants with SMA and healthy controls are being followed over time, and a variety of testing is being conducted to determine whether any reliable biomarkers can be identified for SMA.
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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.
I’ve had symptoms of spinal muscular atrophy since I was a baby. When most children were beginning to walk, my parents noticed that my head would flop to the floor as I crawled. Doctors said I had amyotonia congenita and predicted I wouldn’t live past my 8th birthday. When I turned 14, the diagnosis was changed to benign congenital hypotonia.
It wasn’t until I was leaving for college at age 18 that the label was changed again, to spinal muscular atrophy. These changes didn’t reflect anything new in my condition, but a change in the understanding of the disease called SMA.
While attending Southern Illinois University, in Carbondale, Ill., I earned both my bachelor’s and master’s degrees in psychology and counseling, respectively. After graduation I worked for the Department of Mental Health in New York for 14 years and for the past 20 years have been in private practice as a licensed mental health counselor in Altamonte Springs, Fla. My wife, Sheryl, and I have two grown, adult kids and a young grandson. I also enjoy such hobbies as computer technology and music composition (including the publication of two songs in Nashville).
These pages are designed to help you better understand the causes, symptoms and progression of the different forms of SMA. It’s hoped that this knowledge will help you plan for the future and take heart in the present, knowing that a diagnosis of SMA doesn’t preclude leading a full and rewarding life.
And I’m in no way an exception to the rule. People with SMA are involved in all areas of society: the arts, science, law, management, teaching — you name it. Children with SMA tend to be highly intelligent, creative and adaptable individuals who contribute much to the world despite their challenges.
As you’ll learn from these pages, great progress is being made in treating SMA and moving toward a cure. Medical, computer and assistive technologies enable even very young children to compensate for weak muscles. While some forms of SMA still shorten life span, new approaches to ventilation and feeding have expanded what’s possible. And the search for cures is making steady, encouraging progress.
The Muscular Dystrophy Association is the leading sponsor of SMA research. The Association also provides a full program of services for individuals and families coping with SMA, and up-to-date information about research progress. For more on MDA's services for individuals and families affected by SMA, see Help Through Services .
When I was a baby more than half a century ago, the world was much more discouraging for people with disabilities. Today, medical science, technology, health care services and laws such as the Americans With Disabilities Act help us to stretch to reach our full potential.
If I were to share any words of advice, it would be to let your own experience, rather than a medical label, determine what your life’s limitations and potentials are going to be. Build on your personal strengths, determination and faith — or encourage your child to do so. And remember that the extended family of MDA is there to help when needed. You’re not in this alone.
Throughout my life I’ve been called a dreamer, and I’ve found much joy in fulfilling those dreams. May this also be true for you and your family.
It’s easy to become overwhelmed by news that you or a loved one is affected by spinal muscular atrophy (SMA). That’s why the Muscular Dystrophy Association is here to help. MDA offers a wide range of services  to assist you and your family throughout your journey with SMA.
The first step in connecting with these services is to contact your local MDA office  where dedicated staff stands ready to answer your questions and introduce you to the vast network of support available to you through MDA, including:
In addition to the services listed above, MDA’s public health education program helps you stay abreast of research news, medical findings and disability information through magazines, publications, educational speakers, seminars, videos and newsletters.
Once you contact your local MDA office, you’ll begin receiving Quest , MDA’s award-winning quarterly magazine. Quest publishes detailed articles about research findings, medical and day-to-day care, helpful products and devices, social and family issues, and much more. Other MDA publications can be found at mda.org/publications ; many booklets are available in Spanish.
If you have questions, please know that you have come to the right place by reaching out to MDA. To connect with the MDA office serving your area, please call (800) 572-1717, or enter your ZIP code into the MDA office locator box on this website.
In addition to MDA, a wide range of resources are available to assist with such issues as medical benefits, home modification, accessible travel, employment and more. MDA’s knowledgeable staff maintains resource directories to assist in accessing various federal, state and community-based resources. Please contact the MDA office in your area for assistance with resource referrals, or visit MDA's state-by-state guide  for additional resources in your area.