What is Spinal Muscular Atrophy?
Spinal muscular atrophy (SMA) is a neurological disorder in which degeneration of nerve cells in the spinal cord causes symptoms related to movement, muscle, strength, and movement control. SMA usually first affects the muscles of the head, face, jaw, and neck. It may also affect the limbs.
SMA is one of a group of disorders called motor neuron diseases (MNDs). MNDs affect nerve cells in the brain and the spinal column. Specifically, the diseases attack motor neurons, the nerve cells that control the movement of muscles throughout the body. MNDs cause the neurons to die slowly over time, and as they do, the patient loses the ability to control or use their muscles.
MNDs are classified according to their origin (inherited or not) and which motor neurons they affect. Some MNDs affect cells in the brain (upper motor neurons), and others affect cells in the brain stem and spinal cord (lower motor neurons). SMA affects the lower motor neurons and is usually inherited.
Symptoms of SMA
SMA symptoms primarily affect muscles that control voluntary movements, and muscles close to the center of the body (rather than the limbs) are more likely to be affected. Problems with muscles that control breathing and swallowing may also be affected. Common symptoms include:
- Weakness in the shoulders, upper back, hips, and thighs
- Wasting of muscle tissue (atrophy)
- Curvature of the spine (caused by the weakening of back muscles)
- Difficulty swallowing
- Difficulty breathing
Types of SMA
SMA is classified according to the age of symptoms onset. Types of SMA include:
- SMA Type 1 affects infants younger than six months. It is the most severe form of SMA and is often fatal before age two. This type is also called Werdnig-Hoffmann disease or infantile-onset SMA.
- SMA Type 2 emerges between 6 and 18 months. It is generally less severe than SMA Type 1, but respiratory complications may still be fatal.
- SMA Type 3 affects children older than 18 months. It causes muscle weakness, but children with this type may retain the ability to walk.
- SMA Type 4 affects adults and is less severe than the other types.
Some cases of SMA do not have the same genetic cause as the first four types, and the symptoms of these cases vary widely.
What Causes Spinal Muscular Atrophy?
Most cases of SMA are caused by an abnormal change (mutation) in a gene responsible for protein SMN1’s production. SMN1 plays a role in the communication between motor neurons, and when it is produced in insufficient quantities, the motor neurons die, leading to SMA symptoms.
Is Spinal Muscular Atrophy Hereditary?
SMA is usually inherited in an autosomal recessive pattern. This means a child must inherit two copies of the gene mutation, one from each parent, to develop the disorder. People with only one copy of the mutated gene will not develop SMA, but will be carriers who can pass it on to their children. Two carrier parents have a 25 percent chance of having a child with the SMA with each pregnancy. Half of their pregnancies will produce a carrier, and a quarter will produce a child without mutated genes.
Kennedy’s disease, which is sometimes associated with SMA, is an X-linked disorder. This means that the chance of inheritance varies depending on the sex of the parent and the child. These cases affect males, and females are carriers who don’t develop symptoms of the disorder. Men with the condition will pass the gene mutation to all of their daughters, who will be carriers, but their sons will be unaffected. Female carriers of the mutation will have a carrier daughter 25% of the time, a non-carrier daughter 25% of the time, an affected son 25% of the time, and an unaffected son 25% of the time.
How Is Spinal Muscular Atrophy Detected?
SMA is one of the most common genetic disorders affecting children and is a leading cause of infant death. Early diagnosis of SMA is crucial because early intervention may increase the chances of survival and decrease the chances of severe disability in the future. In 2018, the United States Department of Health and Human Services added SMA to its Recommended Uniform Screening Panel (RUSP), a list of disorders that should be included in states’ newborn screening programs. As of 2022, forty-eight states, excluding Nevada and Hawaii, screened all newborns for SMA.
How Is Spinal Muscular Atrophy Diagnosed?
When your doctor suspects that SMA might be the cause of early symptoms, they will conduct a variety of tests and exams. Much of the diagnostic process is designed to rule out other possible causes of the symptoms rather than directly diagnosing SMA.
- Laboratory tests. Tests of your blood and urine will not necessarily confirm a diagnosis of SMA, but the tests may be able to rule out other conditions that could be causing symptoms.
- Electromyogram (EMG). This test uses electrodes to measure the electrical activity in your muscles as they work. The test can be used to detect abnormalities in muscle function that support a diagnosis of SMA.
- Muscle biopsy. In this test, a small amount of muscle tissue is removed and tested. The biopsy is typically used to detect other diseases and rule out SMA.
- Nerve conduction tests. These tests measure how well your nerves can communicate with your muscles. These tests may detect nerve damage or disorders other than SMA that could be causing symptoms.
- Genetic testing. These tests can identify the gene mutations most often associated with SMA.
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Spinal Muscular Atrophy Treated?
No treatment will stop the progression of SMA or reverse the effects of its symptoms. Instead, most treatments aim to reduce the impact of symptoms, improve quality of life, and prevent life-threatening complications.
Medical treatments for SMA include:
- Nusinersen is a drug approved by the FDA for treating SMA in children and adults. It aims to increase the production of the SMN1 protein and is most effective when administered early.
- Onasemnogene abeparovec-xioi is a gene therapy that introduces a functional SMN gene into the patient’s cells. It has been approved for the treatment of infantile-onset SMA in children under the age of two.
Other therapies used to treat SMA include:
- Speech therapy
- Physical therapy
- Occupational therapy
- Breathing assistance
- Mobility assistance
- Nutritional support
How Does Spinal Muscular Atrophy Progress?
SMA symptoms often worsen over time, and potentially fatal complications can occur in the worst cases. Possible complications include:
- Difficulty swallowing
- Choking or gagging
- Inhaling food, saliva, or other contaminants into the lungs
- Respiratory infections such as pneumonia
Life-threatening complications are most likely in young children with early-onset forms of SMA, but symptoms vary widely.
How Is Spinal Muscular Atrophy Prevented?
There is no known way to prevent SMA.
Spinal Muscular Atrophy Caregiver Tips
A diagnosis of SMA can be devastating, both for the patient and for their families. No treatment will stop the progression of SMA. Instead, most treatments aim to reduce the impact of symptoms, improve quality of life, and prevent life-threatening complications
- Educate yourself about the disease and its effects, and the side effects of medications used to treat it. People with SMA may be at higher risk of developing depression and anxiety. Be on the lookout for the warning signs of these conditions.
- Encourage a healthy lifestyle. There is no cure for SMA, but there are ways to manage symptoms and maintain a good quality of life. Facilitate eating healthy foods and getting as much exercise as possible.
- Join a support group for caregivers. Caregivers are at risk of developing physical and mental health issues, too. So take time for yourself, and get the help you need when you feel overwhelmed.
Spinal Muscular Atrophy Brain Science
Researchers are looking for the causes of SMA, ALS, and other MNDs, for an understanding of how the disease affects the brain, and for effective treatments for the disease. Current studies include:
- Researchers suspect that a brain-cell protein called membralin might play a role in the development of ALS. Scientists don’t know precisely what membralin does in the brain’s nerve cells, but they have found evidence that a protein deficiency may cause ALS and other degenerative nerve diseases. Their studies suggest that gene therapies that increase levels of membralin may have potential as an ALS treatment.
- One clinical study is currently testing a drug that takes a new approach to treating ALS. The drug aims to improve muscle function rather than improve communication between nerves and muscles. The hope is that the drug will help muscles to work more efficiently to compensate for the weakness caused by ALS nerve damage. The drug seems particularly effective at assisting the muscles that control breathing, and patients may breathe better for longer.
Spinal Muscular Atrophy Research
Title: Spinal Cord Stimulation in Spinal Muscular Atrophy (SCSinSMA)
Principal investigator: Marco Capogrosso
University of Pittsburgh
Spinal cord stimulation (SCS) has shown remarkable efficacy in restoring motor function in people with spinal cord injury by recruiting afferent input to enhance the responsiveness of spared neural circuits to residual cortical inputs. This pilot will test if SCS can show evidence to improve motor deficits in people with type 3 or 4 spinal muscular atrophy (SMA). The investigators will enroll up to six subjects with Type 3 or 4 SMA aged 16 or older that show quantifiable motor deficits of the legs but can stand independently. The investigators will then implant the subjects with percutaneous, bilateral, linear spinal leads near the lumbar spinal cord for up to 29 days. Although these leads are not optimized for motor function, but rather for their clinically approved indication of treating pain, the investigators believe they provide a safe technology enabling the research team to perform the scientific measurement necessary to evaluate the potential effects of SCS in motor paralysis with SMA. After the end of the study, the leads will be explanted.
Title: Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen (RISE)
Stage: Not Yet Recruiting
Contact: Millie Young, RNC
Clinic for Special Children
Risdiplam Exchange (RISE) is a study of spinal muscular atrophy (SMA) patients who crossover to 36 months of open-label risdiplam monotherapy following a comparable period of nusinersen treatment. The schedule of assessments (SOAs) carries over seamlessly for the cohort from studies done while treated with nusinersen, and continues to track the most informative outcomes from that trial (e.g., nine-hole peg test and grip strength), while adding the Box and Block Test (BBT) as an additional measure of upper limb endurance and function.
Risdiplam is an orally bioavailable small molecule that distributes into the central nervous system (CNS) and peripheral tissues where it modifies SMN2 pre-mRNA splicing and increases tissue SMN protein levels. It was approved by the U.S. Food and Drug Administration for all SMA patients older than 2 months in August 2020.
Clinical trial data prompted us to consider risdiplam a reasonable alternative to nusinersen administered intrathecally or by subcutaneous intrathecal catheter (SIC) for patients with more advanced SMA. Considered within this clinical context, risdiplam presents a significant advantage by eliminating the risks of mechanical failure, intrathecal bleeding, and CNS infection associated with the SIC device. In addition, the schedule of assessments (SOAs) used in this cohort during the previous three-year period as part of a nusinersen study provides researchers with an established framework for data collection. Thus, the overall clinical experience with risdiplam compared to nusinersen can be assessed using a prospective, crossover design in a real-world setting.
Title: Wearable Technology to Assess Gait Function in SMA and DMD
Principal investigator: Jacqueline Montes, PT, EdD
Columbia University Medical Center
New York, NY
This project aims to devise instrumented insoles capable of accurately measuring gait at each footfall, over multiple hours in any environment. To achieve high accuracy, the investigators will develop a new learning-based calibration framework. Features will be tested in controlled lab settings 39 during a single visit in people with SMA (13), DMD (13), healthy controls (13), and 15 participants in real-life environments.
Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are genetic disorders often resulting in progressive weakness and impaired function. Results from this study will help characterize how gait is affected in SMA and DMD. This novel device can serve as a more affordable and versatile measurement instrument for neuromuscular disorders that affect gait and balance. All participants will be observed and measured while wearing the instrumented insoles in the lab and real-life environments.