August is Spinal Muscular Atrophy (SMA) awareness month. SMA is a disease which affects the motor neurons in the spine, leading to weakness and muscle wasting. It is a genetic disease caused by an abnormality in the survival of motor neuron 1 (SMN1) gene which codes for the SMN protein; this protein is responsible for regulating activities within the cell. A mutation in the SMN1 gene leads to loss of the motor neuron cells which extend from the spinal cord to control different muscle groups and organs. Typically, the loss of these cells leads to progressive weakness in voluntary muscles, often affecting the muscles in the legs, in the arms, and around the lungs first. Next, it begins to affect the muscles of the spine and neck. The effects of SMA are purely physical; it does not affect the ability of the individual to learn or build relationships.
About 1 in 10,000 people are diagnosed with SMA. The mutated gene is autosomal recessive, meaning that both parents must have a mutated gene for their child to have SMA. However, the parents themselves may not be affected—they may only be carriers of the gene. When two individuals who are carriers of an SMN1 mutation have children, there is a 25% chance that their child will have SMA. However, there is a 50% chance that the child will be a carrier of the SMN1 gene mutation but will not have SMA. Additionally, there is a 25% chance that the child will be unaffected. About 2-4% of the time, SMA occurs de novo, meaning that the child develops the mutation without inheriting it from either of his or her parents—it is a new mutation.
The age of disease onset as well as the severity of symptoms are used to classify SMA into several different types. Type 0 is the rarest. Symptoms begin before birth and infants typically only survive a few months. SMA Type 1, also called Werdnig-Hoffmann disease, is the most common, occurring in 60% of SMA cases. It is typically diagnosed during an infant’s first 6 months of life. Babies with SMA Type 1 struggle to breath, cough, and swallow; it is potentially fatal if left untreated.
SMA Type 2 is diagnosed when the child is older than 6 months but less than 2 years old. Often, caretakers are alerted to the issue when the child is delayed in meeting or fails to meet developmental milestones. These individuals typically must use a wheelchair to move around. SMA Type 3 is also known as Kugelberg-Welander disease or juvenile SMA. It is typically diagnosed when the child is between 18 months and 3 years of age, but sometimes diagnosed even during teenage years. Type 3 occurs in about 30% of patients with SMA. It progresses slowly, but individuals may lose their ability to walk at some point during their lives despite having a normal life expectancy. Lastly, SMA Type 4 is adult onset SMA, which occurs in about 5% of SMA patients. Individuals with SMA Type 4 may need walking aids, but other complications are rare.
Other rare forms of SMA include SMA Respiratory Distress (SMARD), Distal SMA, and Kennedy’s disease. All these types are caused by mutations in genes other than the SMN1 gene. SMARD affects the upper spinal cord, causing babies to have weakness in the arms, legs, and respiratory muscles. Distal SMA causes weakness in the hands and feet. Lastly, Kennedy’s Disease is a X-linked disease, meaning that it primarily affects males who inherit the gene from their mother. Appearing between ages 30 and 50, it affects the legs, arms, face, and throat.
When a baby is born in a hospital, a small blood sample is usually taken to test for several genetic conditions. In many states, including Ohio, SMA is among the conditions tested for. This allows treatment to begin before the symptoms appear—research suggests this is when treatment is most effective. Prenatal testing for SMA may also be performed through amniocentesis or Chorionic Villus Sampling (CVS). In amniocentesis, some amniotic fluid—the fluid that surrounds babies during pregnancy—is removed via a needle and syringe from the mother’s uterus to be tested. Chorionic Villus Sampling, a small sample of cells are taken from where the placenta attaches to the wall of the uterus for testing. Both tests screen babies for a plethora of birth defects and genetic conditions, including SMA.
Additionally, potential parents may choose to have themselves tested to see if they are carriers of an SMN1 gene mutation. This is done via a DNA test which can detect 95% of carriers in the general population, but only 70% of carriers in those of African descent. This is due to a hard-to-detect mutation which causes SMA being more common in those of African descent. Those with a family history of SMA may wish to perform carrier screening. For couples who are carriers, they may or may not choose to prenatally test their baby for SMA.
For those who have SMA, there are several treatment options available. The first treatment option is an “SMN-enhancing” approach. Individuals with SMA-causing mutations in the SMN1 gene still have at least one copy of survival motor neuron gene 2 (SMN2). This is a sort of “backup” to the SMN1 gene and produces the SMN protein, but only a portion of the SMN protein produced from SMN2 can be used by the body. An oral medication makes the SMN protein produced by the SMN2 gene more usable by the body by modifying how the gene is spliced. Additional treatments include a spinal injection that modifies the SMN2 gene and a gene therapy treatment which uses a vector to deliver the SMN1 transgene (a transgene is the name of a gene that has been moved from one individual to another).
Also, there are ways to support patients in their struggles to achieve everyday tasks. This includes supporting SMA patients who have muscle weakness in their respiratory system. Patients have increased risk for respiratory infection and may have trouble getting enough oxygen, especially at night. Therefore, their breathing can be supported using non-invasive ventilation (BiPAP) or a tracheostomy (a procedure which creates an alternative air intake hole in the windpipe). These issues are more common among patients with SMA type I or severe SMA type II.
Individuals with SMA may also struggle to get adequate nutrition due to troubles chewing or swallowing. This may require administration of food through a feeding tube or a gastrotomy (a procedure in which an external hole is created in the stomach so that patients can be fed externally through a tube). In addition, SMA patients may experience a need for orthotic devices due to the development of orthopaedic issues such as hip dislocations, scoliosis, or join contracture (shortening of joints). Orthotic devices can be used to aid in walking, increase range of motion, and reduce the risk of fracture.
Although SMA is a rare disease, affecting 1 in 11,000 people born in the United States, SMA is a leading genetic cause of infant mortality; a cure is desperately needed. Currently, researchers are pursuing several avenues to develop a cure. These include SMN1 gene replacement, SMN2 gene alternative splicing, and SMN2 gene activation. Also, researchers are developing methods to stabilize defective SMN proteins, making them able to sustain neurons. Neuroprotective drugs are also being developed which may allow the survival of motor neuron cells even with low levels of SMN protein. Other treatment research focuses on restoring muscle function rather than preserving neuronal cells; these include drugs that stimulate muscles or antibodies that promote muscle growth. Additionally, some private companies have attempted stem cell therapies to cure SMA, but these procedures do not appear to offer any clinical benefit.
Now that you know of the struggles faced by those with SMA, you may wonder how you can help. The first thing you can do is share this article to increase public awareness of the condition. You can share on social media using the hashtags #CureSMA and #SMAAwarenessMonth. You can also participate in an awareness activity such as a candle-lighting event or join the Cure SMA foundation community. More information about SMA, treatment options, and how you can help can be found at curesma.org.
While individuals with SMA may struggle in some areas physically, they still report a high degree of satisfaction with life. Additionally, their cognitive development may occur slightly faster than average, and their intelligence may be above average. The minds and hearts of those with SMA are just like yours and mine—even a bit stronger because of all they have been through.