Spinal muscular atrophy (SMA) is a genetic pathology that attacks nerve cells (motor neurons) in the spinal cord. These are the cells that communicate with voluntary muscles, and as they die, the muscles tend to weaken and atrophy. Voluntary movements such as walking, crawling, breathing, swallowing, or head and neck control can be affected.
More specifically, SMA is an autosomal recessive disease caused by a genetic defect in the SMN1 gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. SMN1 is apparently selectively necessary for survival of motor neurons, as diminished abundance of the protein results in death of neuronal cells in the anterior horn of the spinal cord and subsequent system-wide muscle wasting (atrophy).
Since it is an autosomal recessive disease like cystic fibrosis, both parents must carry the gene, but usually they have no symptoms. Spinal muscular atrophy manifests itself in diverse severity degrees, though general muscle atrophy and mobility impairment are common symptoms in all degrees of severity. It is possible that other bodily systems can also be affected, particularly in early-onset forms of SMA.
Spinal muscular atrophy types and prognosis
There are four different types of spinal muscular atrophy, designated according to the age of onset of symptoms or with the highest attained milestone of motor development: Type I, or Infantile SMA (Werdnig–Hoffmann disease); Type II, or Intermediate SMA (Dubowitz disease); Type III, or Juvenile SMA (Kugelberg–Welander disease); and Type IV, or Adult-onset SMA.
SMA is the most common genetic cause of infant mortality in the world, and is the second most common inherited autosomal recessive disorder. The prognosis is poor for babies with SMA Type I: most die within the first two years. For children with SMA Type II, the prognosis for life expectancy or for independent standing or walking roughly correlates with how old they are when they first begin to experience symptoms — older children tend to have less severe symptoms.
Individuals with SMA Type III may be predisposed to respiratory infections but with proper care it’s possible to have a normal lifespan. Adult-onset SMA usually means only mobility impairment and does not affect life expectancy.
Treatments and new research for SMA
Classified by the FDA as an orphan (meaning rare) disease, there is currently no medical treatment for SMA. Palliative care is given in areas as orthopedics, respiratory care, nutritional care, mobility, cardiology and mental health. The Consensus Statement for Standard of Care in Spinal Muscular Atrophy standardized palliative care for SMA and has been recommended for standard adoption worldwide.
In the last few years research related with SMA has been developing and making some progress. There are some emerging therapies, specially focused on increasing the availability of SMN protein to motor neurons. For example, AveXis, a synthetic biology platform company based in Dallas, Texas, currently developing a gene replacement therapy for SMA.
In addition, the Federally-funded National Institutes of Health’s Between 2003 and 2012, the National Institute of Neurological Disorders and Stroke (NINDS) launched the Spinal Muscular Atrophy Project to expedite therapeutics development for the disease. Clinical trials are ongoing.
The symptoms of SMA are ruled by muscle weakness, but it’s important to note that the disease does not cause nervous system issues, and intelligence is also unaffected. In fact, many physicians experienced with SMA patients have noted that children with the disease tend to be remarkably attentive, interactive, and socially gifted, in spite of the malady.