Prepared by Kathryn J. Swoboda, MD
Director, Pediatric Motor Disorders Research Program, University of Utah School of Medicine

Several years ago, Chang and colleagues published the initial observation that sodium byturate appeared to improve survival and motor function in a mouse model of SMA. Spurred by these observations, Butchbach and colleagues in the Burghes laboratory at Ohio State University subsequently began to painstakingly study other butyrate derivatives. Some of these compounds, when administered early in the course of disease in the SMA animal model, significantly improved survival, but the timing of administration proved critically important. It was clear that the compounds varied in potency, and that any benefit diminished significantly if treatment intervention were delayed. However, one of these butyrate derivatives, sodium phenylbutyrate, had been in clinical use for decades in the treatment of newborn infants with urea cycle disorders. The hypothesis that this compound, given early in the course of the disease, might improve outcomes ultimately resulted in the launch of the STOP SMA study in 2006: a phase I/II open label Study of sodium phenylbutyrate in pre-symptomatic infants with Spinal Muscular Atrophy. These efforts have been generously supported by many: FightSMA, MDA, FSMA, and the Kylee Galbraith Memorial SMA Research Fund at the University of Utah, with medication graciously provided by Ucyclyd Pharma.

We completed enrollment for the STOP SMA trial in April 2010, and early results appear promising: of six infants expected to develop type I, survival and respiratory support needs are considerably improved compared to their affected siblings and symptomatic type I infants in the database, and one infant achieved independent sitting. In addition, two of six children expected to develop type II disease achieved independent walking. In addition to the improved motor outcomes, electrophysiologic data indicate that these children have less significant denervation than expected for age based on a natural history studies. However, the next few months will undoubtedly prove critical in moving this work forward to achieve the ultimate goal of this project: demonstrating the feasibility of rapid identification of newborns with SMA in order to permit early intervention for the many promising new therapies on the horizon.

Over the next year, we anticipate completion of the final dataset for the STOP SMA trial, data analysis and dissemination, development of a STOP SMA trial registry and database for prospectively identified SMA subjects, and planning for the next steps forward to identify infants via newborn screening, using a recently validated pilot newborn screening assay. For the STOP SMA protocol, we developed a proactive monitoring program with protocol-driven interventions for nutrition and respiratory care, modeled after the current cystic fibrosis clinic model. However, further pilot studies are necessary to determine how to best implement such a program in several states in anticipation of the launch of a nationwide prospective newborn follow-up program in infants diagnosed with SMA on newborn screening. Development of this database, and dissemination of best practices and proactive monitoring protocols to physicians and parents will improve the quality and length of life and the standard of care provided to children with SMA. We are extremely grateful for the additional funds provided via the Pepsi Challenge, Stop SMA and FightSMA at this crucial time to move this project forward as quickly and efficiently as possible.

Kathryn J. Swoboda, MD
Associate Professor, Neurology and Pediatrics
Diplomate, American Board of Medical Genetics
Director, Pediatric Motor Disorders Research Program
University of Utah School of Medicine

Sarah Kennedy had just given birth to her second daughter last December when her 16 month old daughter, Brielle, was diagnosed with spinal muscular atrophy (SMA) type II. Five days after hearing this devastating news, her husband Eric was deployed to Afghanistan with the Army. While they were apart, Eric and Sarah were forced into action to determine how best to care for Brielle and also to deal with the possibility that the new baby, Brooke, may also be affected by the disease. While Eric was deployed, Sarah tackled the heavy work of contacting doctors and therapists and creating a plan for Brielle’s treatment and on top of all that, decided to have Brooke tested. When Brooke also tested positive for SMA type II, she was enrolled in the “Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants with Spinal Muscular Atrophy” (or “STOP SMA”) study being conducted by Dr. Kathryn Swoboda at the University of Utah, with funding from FightSMA.

Brielle with Chad Knaus

The extended Kennedy Family became involved with the larger SMA community, participating in fundraisers and contacting their Congressional Representatives about the SMA Treatment Acceleration Act. Sarah’s sister in North Carolina, Christen, introduced her co-workers at Hendrick Motorsports to SMA. After meeting Brielle for the first time at a race in Michigan, (with Christen’s help), Chad Knaus, the crew chief for three-time NASCAR Sprint Cup Champion driver Jimmie Johnson, became interested in this little known disease and asked what he could do to help raise awareness.

Chad started by adding informational links about the disease to his personal website, but recently he has gone a step further. Chad will be sponsoring a hole at the upcoming Jimmie Johnson Foundation Annual Golf Tournament and has chosen to include the FightSMA logo on the sign posted at the sponsored hole. We thank Chad Knaus and the Jimmie Johnson Foundation for including FightSMA and for this wonderful opportunity to raise awareness of SMA.

The Virginian-Pilot newspaper printed a story Sunday about the family leading FightSMA’s chapter in Virginia Beach, Virginia. The article touched on aspects that many families affected by spinal muscular atrophy (SMA) face: the shock of the diagnosis, the struggle to fight the disease, and the loss of a child. But, the article also recognized the promise and hope brought about by research being done around the country and the need for the fight to continue.

The Saville Family openly speaks about their experience of learning their daughter Morgan had SMA, of raising awareness and funding, of seeking treatment, and of her death in 2005. They also discuss how their efforts to defeat SMA have been renewed following their new baby’s birth, diagnosis, and enrollment in Dr. Kathy Swoboda’s pre-symptomatic study, funded in part by FightSMA. Stacy Saville and her son, accompanied by Virginian-Pilot photographer Genevieve Ross, attended the FightSMA Annual Conference in April and traveled to Capitol Hill to advocate for the SMA Treatment Acceleration Act.

To read the full article, click here. Below is a lovely slide show that the paper also put together.

FightSMA is providing funding for a new study called “Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants with Spinal Muscular Atrophy” or “STOP SMA” being conducted by the laboratory of Dr. Kathy Swoboda at University of Utah School of Medicine. The study will assess the safety, tolerability and potential efficacy of sodium phenylbutyrate (NaPB) in presymptomatic infants genetically confirmed to have SMA.

Sodium phenylbutyrate (NaPB) is a medicine that has been used for many years to treat patients with urea cycle disorders. Recent research suggests that NaPB may be able to prolong survival in animal models of motor-neuron disease. In addition, pilot data in human infants have suggested a possible benefit of early administration of NaPB. Since significant motor-neuron loss occurs in the first few weeks to months of life in the most severely affected infants, the earlier that NaPB treatment can be started, the greater the potential benefit in delaying onset and lessening severity of SMA symptoms.

For more information about this study, including eligibility criteria, and for links to other clinical trials, please visit the FightSMA website.