WHAT IS SPINAL MUSCULAR ATROPHY?

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.

HOW DOES IT AFFECT CHILDREN?

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.

HOW COMMON IS SMA?

In addition to its severity, SMA is a relatively common genetic disease. 1 in 40 Americans are carriers, or approximately 7 million people. Over 25,000 Americans are believed to suffer from SMA, comparable in prevalence to better-known diseases such as ALS (Lou Gehrig's Disease) and Cystic Fibrosis.  The incidence of SMA, an estimated one in every 6,000 live births, is similar to Duchenne Muscular Dystrophy and Tay Sachs Disease (in the Jewish population).

WHY IS AWARENESS SO LOW?

In severe cases, SMA kills in the womb or early in infancy, resulting in under-diagnosis. Even in less severe forms, SMA was historically difficult to diagnose, since symptoms and age of disease onset vary tremendously. In fact, until recent advances pinpointed the genetic cause, SMA was believed to be a family of related diseases rather than one disease. However, a string of scientific breakthroughs over the past seven years have dramatically improved understanding of the disease, as well as revealed how common and deadly it is.
 

WHY IS THE RESEARCH OUTLOOK SO PROMISING?

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 these remarkable advances of the past fifteen years, scientists now believe SMA may have a greater probability of realizing 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.  While small compared to the amounts spent by NIH on many other diseases of comparable prevalence and severity, the requested funding amount is substantially greater than current funding for SMA of $15 million.

WHAT IS CURRENTLY BEING DONE?

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. The program is proceeding well and the next step will be to advance compounds from the SMA translation pilot into the clinic trails.

WHAT ARE THE DIFFERENT FORMS OF SMA?

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

Type I Acute SMA (Werdnig-Hoffman Disease): Affects the bulbar muscles of infants in the womb or shortly after birth. Victims typically exhibit limited movement, and 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.

Type II Intermediate SMA: Symptoms usually emerge from six months through age two, and the progression of symptoms varies greatly. Muscle weakness and respiratory infections are typical. 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 appear between two and 17 years of age. Those afflicted can often exhibit difficulty walking, mild muscle weakness and are at risk for respiratory infections. Most afflicted live into adulthood.

Less common forms of SMA 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 causes breast enlargement called gynecomastia.

HOW IS SMA DIAGNOSED?

Medical experts believe that a blood test screening for the deletion of the gene called Survival Motor Neuron (SMN) can typically 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.

HOW ARE SMA VICTIMS CARED FOR?

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.