The annual SMA Researcher Meeting is the largest research meeting in the world specifically focused on SMA. This year, we had a record setting 735 attendees join together in Anaheim, CA. The goal of the meeting is to create open communication of early, unpublished data, accelerating the pace of research. The meeting also furthers research by building collaborations—including cross-disciplinary dialogue, partnerships, integration of new researchers and drug companies, and educational opportunities for junior researchers.

This is the third in a series of summaries from our 2019 researcher meeting, highlighting the most interesting new discoveries presented there. This update covers the session entitled, “Clinical Research Studies for SMA”, moderated by Dr. Tom Crawford (Johns Hopkins University).

The first talks of the session were focused on biomarkers, measurable indicators of the severity or presence of a disease state. To begin, Dr. Robert Bowser (Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center) gave a plenary talk in which he described fluid-based biomarkers for ALS. Next, Dr. Tom Crawford spoke about the development of phosphorylated neurofilament (pNF) as a biomarker for SMA. Specifically, he discussed the comparison of neurofilament light chain (pNF-L) and neurofilament heavy chain (pNF-H) concentrations in the cerebrospinal fluid in individuals enrolled in the Nusinersen trials. The study found that CSF pNF-L and pNF-H levels appear highest in presymptomatic SMA participants with 2 SMN2 copies and lowest in those with later-onset SMA. Dr. Charlotte Sumner (Johns Hopkins University) followed with a talk about pNF-H and motor function achievement in Nusinersen-treated individuals. She found the pNF-H levels were elevated at baseline in individuals with SMA and that Nusinersen treatment reduced pNF-H to lower levels. Lower levels or greater decreases in pNF-H levels during the Nusinersen loading phase appear to be predictive of subsequent motor function with those with lower levels or greater decreases having greater function. However, further evaluation is needed.

Dr. Jacqueline Montes (Columbia University) gave a presentation about diminished muscle oxygenation during exercise in ambulatory SMA patients. In addition to demonstrating that individuals with SMA demonstrate diminished muscle oxygenation when exercising, she suggested that evaluating the metabolic pathways used by muscle during exercise in persons with SMA warrants further study as it may relate to fatigue, impaired endurance, and functional limitations. The next talk, given by Dr. Bart Bartels (University Medical Center Utrecht, Netherlands) discussed the endurance shuttle tests as outcome measures for fatigability in SMA. He found that the endurance shuttle tests are reliable and valid outcome parameters to measure endurance and that they are applicable to the wide clinical spectrum of SMA. Dr. Lindsay Alfano (Nationwide Children’s Hospital) spoke about the development of the Neuromuscular Gross Motor Outcome (GRO) as an assessment tool that can evaluate motor skills of all ages and abilities to allow for continuous longitudinal monitoring of individuals using the same motor function scale. Next, Dr. Linda Lowes (Nationwide Children’s Hospital) described her use of the ACTIVE-mini, an assessment tool for tracking spontaneous upper and lower limb movement to assess infants with type 1 SMA having 2 copies of SMN2. She found that all the infants with SMA demonstrated significantly different movements from those of infants in the control cohort. These differences were detected as early as 12 days of age supporting her group’s hypothesis that motor decline begins before a child exhibits visible weakness or motor delay. In the last talk of the session, Dr. Katlyn McGrattan (Boston Children’s Hospital) described her work using instrumental swallowing assessments to capture the natural history of physiologic swallowing deficits in SMA type 1. She found that infants with SMA type 1 exhibit profound deficits in swallowing early in disease progression and that utilization of swallowing assessments to guide dysphagia treatment regimens early in disease progression may improve infant health outcomes.