Spinal Muscular Atrophy (SMA) Program | Research & Innovation

Boston Children’s Hospital is known for pioneering new treatments and has the world’s largest research program at a pediatric institution. We have been active in both clinical and laboratory research on spinal muscular atrophy (SMA) since 2004, under the leadership of SMA Program Director, Basil Darras, MD.

Nusinersen (Spinraza™) clinical trials

Nusinersen, formerly known as SMNRx, is a drug that has been shown to increase the survival of motor neurons that die off in SMA, robbing children of muscle control. The drug compensates for the effects of the SMN1 mutation by rallying a “backup” gene, known as SMN2. SMN2, like SMN1, also makes the SMN protein needed to keep motor neurons healthy, but most of it is truncated and nonfunctional. Nusinersen uses a genetically based technology called antisense oligonucleotide to shore up this backup gene. This enables people to make more of the full-length, functional SMN protein. 

Boston Children’s has been involved in clinical trials of nusinersen, sponsored by Ionis Pharmaceuticals, since they were first initiated in 2011. We were the first in the world to enroll a child with SMA Type 1 in the Phase 3 ENDEAR trial, in 2014. This trial enrolled infants under 7 months of age and randomly assigned them to receive nusinersen, given by injection into the spinal canal through a lumbar puncture or placebo (a “fake” lumbar puncture). In an interim analysis, 40 percent of babies given nusinersen — versus none of the babies given placebo — achieved some improvement in motor milestones (head control, rolling over, sitting, standing and, in a few cases, walking with support). The trial was stopped in August 2016 because of positive findings.

A second trial, called CHERISH, evaluated nusinersen in children with type 2 SMA ages 2 to 12 who had the ability to sit independently but not walk independently. Children receiving nusinersen showed improved motor function, and this trial was also stopped due to positive findings, in November 2016.

Because of these positive results, the Food and Drug Administration gave nusinersen priority review status and approved the drug in December 2016 for all forms of SMA. The drug has been marketed by Biogen under the brand name Spinraza™.

How nusinersen works

SMN1, the gene mutated in spinal muscular atrophy, has a backup — SMN2 — that can also produce the SMN protein. But SMN2 has a small “letter” change (from C to T) that causes an entire coding region, exon 7, to be spliced out. As a result, the protein it makes is truncated and not fully functional. Nusinersen is an antisense oligonucleotide — a small string of nucleotides that target SMN2’s pre-messenger RNA. It prevents exon 7 from being spliced out, allowing SMN2 to make full-length SMN protein. (Credit: Neurology 2016 Mar 8; 86: 890–97; doi: 10.1212/WNL.0000000000002445.)

SMA Natural History Study

To help families plan for their children’s future and provide a benchmark for evaluating new treatments, Boston Children’s has been involved in long-term studies since 2005 to track the progression, or “natural history,” of SMA over time. The SMA Natural History Study, supported by the SMA Foundation, evaluated children with SMA Types 1, 2 and 3 every two to six months, testing muscle strength, motor function, muscle mass, respiratory function and quality of life. This study was conducted through the Pediatric Neuromuscular Clinical Research (PNCR) Network, together with Columbia University Medical Center, Children’s Hospital of Philadelphia and the University of Rochester Medical Center.

Visit PubMed to view abstracts about our clinical SMA research.

Outcome measures

When researchers and physicians conduct clinical trials of new drugs and therapies, they need to have standardized systems for measuring the symptoms of children with SMA so they can know whether the new therapy is helping. Investigators in the Boston Children's Spinal Muscular Atrophy Research Program, together with the other members of the PNCR network, have been active in developing outcome measures. Some of these have been used in SMA clinical trials such as ENDEAR and CHERISH.

Basic scientific studies


Researchers at Boston Children’s and elsewhere are working to better understand SMA at the cellular and molecular level. Boston Children’s neurologist Mustafa Sahin, MD, PhD, for example, has been studying proteins that are associated with the SMN protein as well as genetic regulatory factors that may influence motor neuron function.