SMA is a deadly and relatively common genetic disease and is the leading genetic cause of death in infants and toddlers. It is the absence/defect in the Survival Motor Neuron Gene (SMN1) that causes Spinal Muscular Atrophy. The SMN1 gene codes for survival of motor neuron (SMN) protein, and this protein is critical to the survival and health of motor neurons, nerve cells in our spinal cord that our brain uses to control our muscles. Without sufficient SMN protein, motor neurons shrink and die. As the motor neuron network breaks down, the ability of the brain to control muscles diminishes and with less control and use, muscles weaken and waste away.

The decline of the motor neuron network, and the increased demand placed upon remaining motor neurons by children’s growing bodies, results in a progressive loss of muscle control and movement. In severe cases, the weakness is so great that death results either in the womb or within the first two years of life. Even in milder forms, SMA has a devastating and deadly impact on children. Victims either never acquire, or progressively lose, the ability to walk, stand, sit and eventually move. Children suffer increasing bone deformities, spinal deformities and ultimately fatal respiratory complications. Repeated surgery is often required to prolong life, which may include procedures such as tracheotomies to assist in breathing and eating and spinal fusion to mitigate spinal damage. Children's minds are unaffected, however, leaving their developing brains trapped in weakening bodies.

Dramatic breakthroughs have been made in the past fifteen years, catapulting SMA from being poorly understood to being on the threshold of treatment. First, the relevant gene (SMN1) responsible for the disease was identified, followed by discovery of the key protein it makes (SMN protein) and its importance to motor neurons. Perhaps most importantly, scientists discovered a partially functioning ‘backup gene’ (SMN2), which makes approximately 10 percent of the same critical protein. Research is focused on drugs and genetic therapies that appear likely to ‘up-regulate’ (improve function of) the functioning backup gene; the greater the amount of functional SMN protein produced by SMN2, the more motor neurons can be supported and kept healthy. Scientists have already identified drugs that appear promising and are now in the process of testing these leads.

Given the remarkable advances of the past fifteen years, scientists now believe SMA may have a greater probability of realizing a treatment or cure than any other major genetic disease. However, development of these treatments within the next few years would likely require $20-30 million of annual research funding. The SMA community is actively working to achieve that funding goal.

NIH has selected SMA as a model for a new approach to funding translational research. Translational research develops findings made by scientists in the lab into drugs and treatments that doctors can use to save the lives of patients. SMA was chosen due to the fact that it 1) offers a high probability of developing treatment or cure, 2) is relatively common, 3) is a devastating children's disease, and 4) has no current treatment.
As a result of its investment in the translational research project, NINDS funding for SMA research has reached approximately $13 million annually. [For more information about the NINDS translational research project, please visit the SMA Project website.]  Additional funding for investigators is provided by patient advocacy organizations in the US and worldwide. These funds support investigators at world-renowned research centers, including University of Pennsylvania, Johns Hopkins, Columbia University, Ohio State, MIT, University of California, Arizona State, Stanford University, and Harvard University. New research dollars are also being invested in early biotech and pharmaceutical projects to speed progress toward a treatment.

The disease has a wide range of impact on children. Common forms of childhood- or juvenile-onset SMA are:

Type I Acute SMA (Werdnig-Hoffmann Disease): Affects the respiratory or breathing muscles of infants in the womb or shortly after birth. Victims typically exhibit limited movement and have difficulty holding their head straight, feeding and swallowing. Reduced strength in the chest muscles often results in labored breathing with the chest appearing sunken. The progressive weakening of the muscles leads to respiratory infections and eventual death, usually by the age of two.  More than 50% of patients with SMA have this form of the disease.

Type II Intermediate SMA: Symptoms usually emerge in patients between six and eighteen months, and the progression of symptoms varies greatly. Muscle weakness and respiratory infections are typical. Infants and children with this form of the disease are at one time able to sit independently.  Due to the varied progression of symptoms, life expectancy ranges from early childhood to adulthood.

Type III Mild SMA (Kugelberg-Welander or Juvenile Spinal Muscular Atrophy): Symptoms typically appear between eighteen months and early adulthood. Those afflicted often exhibit difficulty walking, mild muscle weakness and are at risk for respiratory infections. Most afflicted live into adulthood and have a life expectancy that is close to normal.

Less common forms of SMA afflict adults and are characterized by a slower progression of symptoms. These forms include:
Type IV Adult Onset SMA: Symptoms typically emerge after age 35. Type IV is characterized by the subtle onset and slower progression of symptoms, particularly difficulty walking.
Adult Onset X-Linked SMA: (Kennedy's Syndrome or Bulbo-Spinal Muscular Atrophy): Occurs only in males and affects facial and tongue muscles and often causes breast enlargement known as gynecomastia.

A simple blood test that screens for deletion of the gene called survival motor neuron (SMN1) is typically used to diagnose SMA. If symptoms are exhibited and there is no indication of gene deletion, a muscle biopsy and/or electromyography (EMG) may be necessary to confirm the diagnosis.

Those afflicted with SMA need constant, ongoing care from a variety of specialists including neurologists, orthopedists and pulmonologists, as well as repeated surgical procedures for bone and spinal weakness. Ongoing physical therapy utilizing exercise, stretching and strengthening may help maximize function, mobility, safety and comfort for SMA victims. In addition, an experienced occupational therapist can work with SMA victims to integrate the progression of their disease into their lives.