The Annual SMA Researcher Meeting is the largest research meeting in the world specifically focused on SMA. This year we had a record setting 470 attendees. The goal of the meeting is to create open communication of early, unpublished data, accelerating the pace of research.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.
We are posting a series of summaries from our 2017 researcher meeting, highlighting the most interesting new discoveries presented there. This update covers the session entitled, “Clinical Research Studies for SMA”, moderated by Dr. Kathryn Swoboda, MD, Cure SMA scientific advisory board.
The session began with two talks focused on outcome measures for clinical trials. Jacqueline Montes, Columbia University, described age-related patterns of progression in ambulatory function in SMA. Using the six minute walk test (6MWT), she saw that young ambulant patients gain skills while in adolescence and early adulthood patients lose function. She recommended using the 6MWT as a primary outcome measure in future clinical studies targeting ambulatory patients.
Next, Linda Lowes, Nationwide Children’s Hospital Ohio, gave a talk about the use of ACTIVE, a test of workspace volume (WSV) developed for use across the lifespan regardless of ambulatory status. Her study focused on determining the relationship between WSV as measured by ACTIVE and the Patient Reported Outcomes Measurement Information System (PROMIS) parent reported measure of upper extremity function. Data collected from her study indicate that WSV measured by ACTIVE highly correlates with PROMIS and thus, should be considered as an outcome measure in clinical trials.
The next talk by Christian Czech, Roche, described an observational study comparing qualitative and quantitative muscle MRI measures with clinical scores and molecular parameters in ambulatory SMA patients. MRI data collected by his group showed that all thigh muscles were affected by SMA with a reduced cross-sectional area and residual muscle. The MRI measures showed strong correlation with motor function assessments such as the 6MWT and thus, may be used as predictors of motor function in SMA patients.
The next talk, given by Bart Bartels, University Medical Center Utrecht, focused on fatigablility, defined as the decline in performance during and after prolonged motor tasks, and its emergence as an important complaint among patients with SMA. In his talk, Dr. Bartels described the use of the Endurance Shuttle Box and Block Test (ESBBT) to determine fatigability in the upper limb in patients with SMA. He found the SMA patients demonstrated a reduced endurance capacity on the ESBBT in comparison to healthy controls and that these patients also showed an abnormal response in surface EMG.
In the next talk, Seward Rutkove, Harvard Medical School, investigated electrical impedance myography (EIM) as a biomarker to assess muscle status in infants with SMA. Using the data collected in the NeuroNEXT study, the characteristics of EIM in healthy and SMA infants were compared with that of older children and adults. It was found that the data is able to discriminate healthy from SMA children at baseline suggesting that further analysis is needed to apply EIM to clinical trials involving infants and that EIM may be used a biomarker for assessment of therapies for individual patient care.
The last two talks of the session were focused on newborn screening for SMA. The first of these was given by John Staropoli, Biogen. He presented data on a pilot NBS study conducted in Taiwan where 144,509 newborns were screened with a PCR-based assay with 8 infants screening positive for SMA. These 8 SMA cases demonstrated proof of concept for SMA newborn screening and together with clinical trial data support for the need for early identification and treatment of infants with SMA. In the final talk, Robert Vogt, Centers for Disease Control and Prevention, described the development of a new newborn screening assay to detect SMN1 exon 7 deletion. This assay can be multiplexed (run at the same time) as the assay used to detect SCID, an immune disorder. The ability to multiplex these tests reduces costs of testing and help to eliminate the need for additional testing equipment.