SMA is caused by a mutation in the survival motor neuron gene 1 (SMN1). In a healthy person, this gene produces a protein—called survival motor neuron protein or SMN protein—that is critical to the function of the nerves that control our muscles. Without it, those nerve cells cannot properly function and eventually die, leading to debilitating and often fatal muscle weakness.

After the discovery of the SMN1 gene and SMN2, the SMA “backup gene,” by Judith Melki, researchers began working on the idea that SMA could be treated by targeting this SMN2 gene. Due to a splicing error—discovered by Dr. Umrao Monani in the laboratory of Arthur Burghes and Dr. Chris Lorson in the laboratory of Elliot Androphy, in work funded by Cure SMA—most of the SMN protein made by SMN2 is missing an important piece, called exon 7.

This means SMN2 cannot make enough complete SMN protein to fully make up for the missing or faulty SMN1 gene. Researchers wanted to see if there was a way to fix the splicing of SMN2, to cause it to make more complete SMN protein.

Cure SMA Provides Seed Funding

From 2003 to 2006, Cure SMA provided the very first research funding needed to begin investigation into this approach. In work funded by Cure SMA, Drs. Ravindra Singh and Elliot Androphy identified a gene sequence called ISSN1, which could be targeted by a drug to treat SMA.

Drs. Adrian Krainer, Yimin Hua and their colleagues at Cold Spring Harbor Laboratory then built upon this work. They spent several years researching this gene sequence and how it could be targeted to help treat SMA. Then, in 2010, a pharmaceutical company called Ionis licensed this work to begin testing Spinraza, then called Nusinersen.

Ionis started the first clinical trial in 2011, and entered into an agreement with Biogen in 2012 to continue testing the drug. Over the next few years, the drug passed successfully through phase 1, phase 2 and phase 3 clinical trials—a journey that few drugs are able to make. Researchers will often test thousands of compounds to produce one drug for clinical trials. And of the drugs that start clinical trials, only 10% will make it to FDA approval.

On August 1, 2016, Biogen and Ionis announced that Spinraza had met its primary endpoint in ENDEAR, one of its two pivotal trials. Because of this, Biogen and Ionis filed a New Drug Application, requesting FDA approval for the drug.

On December 23, 2016, the FDA announced that it had approved Spinraza for SMA, making it the first-ever approved therapy for SMA.

We would like to thank and acknowledge Cold Spring Harbor Laboratory (CSHL) and the University of Massachusetts Medical School for generating critical intellectual property for the program that was licensed to Ionis Pharmaceuticals. We specifically thank Drs. Adrian Krainer, Yimin Hua and colleagues at CSHL for years of dedication to and hard work on the preclinical development of Spinraza for SMA, and Drs. Ravindra Singh and Elliot Androphy for their work funded by Cure SMA in originally identifying the ISSN1 gene sequence, which is the sequence targeted in Spinraza.