Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease characterized by muscle atrophy and weakness. The disease generally manifests early in life and is the leading genetic cause of death in infants and toddlers. SMA is caused by defects in the Survival Motor Neuron 1 (SMN1) gene that encodes the SMN protein. The SMN protein is critical to the health and survival of the nerve cells in the spinal cord responsible for muscle contraction (motor neurons).
SMA has generally been believed to affect as many as 10,000 to 25,000 children and adults in the United States, and therefore it is one of the most common rare diseases. One in 6,000 to one in 10,000 children are born with the disease. One in 40 to one in 50 people (approximately 6 million Americans) are carriers of the SMA gene. SMA is an autosomal recessive genetic disease, meaning that a person must have two copies of a defective gene to have the disease. SMA carriers do not exhibit SMA symptoms, but do carry a defective copy of the SMN1 gene. If both parents are carriers of the SMA gene, then each of their children has a 1 in 4 chance of having the disease. SMA has multiple forms which vary in severity. The most severe form (Type I) manifests before 6 months of age and generally results in death before age two. Patients with milder forms of SMA may not have symptoms of muscle weakness until much later in childhood or even as adults. The SMA Foundation has prepared a number of informational materials about the disease and the care of SMA patients.
The genetics of SMA provides a unique opportunity for therapeutic development. While SMA patients lack the functional SMN1 gene, they do have a “backup” gene, SMN2. SMN2 also makes SMN protein, but at greatly reduced efficiency, leading to lower than normal levels of the protein. SMN2 provides an attractive target for developing SMA therapeutics, and the majority of drug development efforts in the field are focused on increasing SMN protein production from this gene.