Since 1995, scientists have known that a deficiency of functional SMN protein (SMN stands for survival of motor neuron) is the underlying cause of chromosome 5 SMA. Two nearly identical genes carry the genetic instructions for making SMN protein: SMN1 and SMN2. Proteins made from the SMN1 gene are full-length, functional, and appear to be necessary for the survival and proper function of motor neurons. By contrast, proteins made using instructions from the SMN2 gene are shorter and tend to be less stable but can compensate for a lack of SMN protein when the SMN1 gene is not functioning.

In SMA types 0 through 4, flaws (mutations) in each of the two copies of the SMN1 genes result in insufficient production of full-length, functional SMN protein. Fortunately, a certain amount of full-length SMN protein can be made from the SMN2 gene. Many people have multiple copies of the SMN2 gene. These extra SMN2 copies can lessen the impact of a flaw in both SMN1 copies. In chromosome 5-related SMA, the more copies of SMN2 a person has, the milder the course of SMA is likely to be.

Researchers are seeking to exploit this unique redundancy through development of strategies that restore levels of full-length SMN protein.”

MDS Muscular Dystrophy Association (https://www.mda.org/disease/spinal-muscular-atrophy/research)