OVERVIEW

SMA may provide one of the first returns on our national investment in genome research. A series of breathtaking discoveries over the past decade have catapulted the disease to the threshold of potential treatment or cure. These discoveries have transformed SMA from a poorly understood condition into a disease that may have greater probability of treatment than perhaps any other major genetic disease. As always, luck has played a remarkable role, as these discoveries have been made despite negligible support from NIH and the Federal government. Fortunately, scientific good luck and the relentless effort of families devastated by SMA enabled remarkable advances. Today, Spinal Muscular Atrophy has potential to be the first major genetic neurological disease to be effectively treated or cured.

THE ADVANCED STATE OF SMA RESEARCH

For most severe genetic or neurological diseases, science is still at relatively early stages. Remarkably, in the case of SMA, enormous amounts of critical knowledge have been uncovered, and the apparent medical challenge appears quite simple relative to many other diseases.

1. The nature of the condition is understood: Motor Neurons shrink and die

2. The damage has been found to directly correlate to, and be caused, by the absence of a single protein (SMN Protein), which has been identified

3. The gene responsible for production of this protein has been identified (SMN1 Gene)

4. Remarkably, a functioning 'backup' gene (SMN2 Gene) has been found, which also produces approximately 10 percent of the critical protein. Building a missing gene, or inserting a completely missing protein product is extraordinarily complex and is the challenge faced in most comparable genetic diseases. However, improving the function of an existing gene that is already producing protein is a dramatically simpler task.

5. Animal (mouse) models have been developed for SMA, allowing for screening / testing of potential drugs

6. High throughput screening has resulted in leads on compounds that appear promising in 'up regulating' (improving function of) the SMN2 Gene and its production of SMN Protein.

7. Compound screening in mouse models is underway.  The results of these studies will demonstrate provide “proof-of-concept” evidence need for further development efforts.

Overall, research for many other severe diseases is at stages 1-3. Through the string of discoveries in the past seven years, SMA research has advanced to an extraordinarily advanced state. With proper focus and funding, treatments appear imminent. 'Luck' has resulted in a remarkable scientific foundation that could be built upon to produce effective treatments in the near future.