In 2016, the spinal muscular atrophy community celebrated the approval of the first-ever treatment that targets the underlying genetic cause of SMA. This was a milestone more than 100 years in the making, made possible by dedicated researchers, and the community that supported their work.
The Discovery of SMA
SMA was first described by a German scientist named Johann Hoffman, and an Austrian scientist named Guido Werdnig. Both men had noticed several cases of babies developing muscle weakness within the first few months of life. They also noticed that this condition seemed to run in families.
As they investigated this mystery condition, they saw that the motor neuron cells in these babies seemed to degenerate, specifically in a section of the spinal cord known as the anterior horn. This section is located toward the front of the spinal cord, and is associated with the skeletal muscles—unlike other sections of the spinal cord, which are associated with touch and other senses.
Their observations led to the identification of spinal muscular atrophy. To this day, SMA type 1 is often called Werdnig-Hoffman disease, in recognition of these two scientists.
A few decades later, two other scientists, Erik Kugelberg and Lisa Welander, were able to differentiate the later onset forms of SMA from other similar diseases like muscular dystrophy. This is why SMA type 3 is also called Kugelberg-Welander disease.
From Discovery to Treatment
Drs. Werdnig and Hoffman first made their discovery in the 1890s, but it would be another century before the next major discovery in SMA was made. During the 1900s, scientists made major advances in our understanding of human genetics, including the discovery of DNA. These discoveries helped increase our knowledge of many diseases, including SMA.
In 1995, Dr. Judith Melki and her team identified and determined the DNA composition of the survival motor neuron gene 1 (SMN1). They demonstrated that, in individuals with SMA, this gene was deleted or mutated. Dr. Melki also identified the SMN2 gene, the SMA “back-up gene.” Four years later, in 1999, Dr. Umrao Monani in the laboratory of Arthur Burghes, and Dr. Chris Lorson in the laboratory of Elliot Androphy described the splicing error in SMN2. This work was funded by Cure SMA.
The discovery of SMN1 opened up the door for a genetic test to confirm the SMA diagnosis. Prior to this, the diagnosis was made based on the visible signs and symptoms of SMA.
The discoveries of SMN1 and SMN2 also opened up the door for new treatments to be discovered. In 2003, just a few years after Drs. Monani and Lorson identified the splicing error in SMN2, Cure SMA made the very first research grant to Dr. Ravindra Singh in the laboratory of Elliot Androphy to study an approach that would fix the splicing of SMN2.
This approach eventually led the discovery and development of Spinraza by Frank Bennet at Ionis and Adrian Krainer at Cold Spring Harbor Laboratory, which was approved by the FDA in December 2016.
Also in 2016, Cure SMA honored Judith Melki at the Annual SMA Conference, for her important contributions to our understanding of SMA. Each year, the Annual SMA Conference brings together hundreds of scientists who are investigating new questions about SMA. They are building on the discoveries of Drs. Werdnig, Hoffman and Melki, hoping to develop more treatments for all types, ages and stages of SMA.
Our thanks to the smart and determined researchers who are working each day on behalf of our community.