Table 2.
Interview questions and advisor responses
| Survey Question and Responses | Group Score (0–5) or Response (%) |
| Initial/Pre-call survey | |
| Please rank the following types of biomarkers in order of your interest.1 | |
| Biomolecular (i.e., SMN protein, neurofilament, muscle markers)....... | 4.7 |
| Electrophysiological (i.e., CMAP, MUNE, EIM, etc.)....... | 3.6 |
| Genetic factors (i.e., SMN2 copy number, SMN2 polymorphisms, modifier genes)....... | 3.1 |
| Transcription and splicing regulators (i.e., miRNAs, methylation factors, lncRNAs)....... | 3.0 |
| Muscle imaging (i.e., MRI, ultrasound)....... | 2.7 |
| Which biomolecular biomarker candidates are you most interested in exploring?2 | |
| Neurofilament | 100.0% |
| SMN protein | 75.0% |
| Creatinine | 50.0% |
| Creatine kinase or other markers of muscle damage | 50.0% |
| Which electrophysiological biomarker candidates are you most interested in exploring?2 | |
| CMAP | 83.3% |
| MUNE | 83.3% |
| EIM | 66.7% |
| Repetitive nerve stimulation | 66.7% |
| Electromyography | 50.0% |
| Survey One | |
| Which candidate would be the best pharmacodynamic biomarker… 3 | |
| …in infants | |
| Neurofilament | 72.7% |
| CMAP | 63.6% |
| SMN protein | 45.5% |
| …in children and teens | |
| Neurofilament | 63.6% |
| SMN protein | 54.5% |
| CMAP | 45.5% |
| …in adults | |
| CMAP | 54.5% |
| Neurofilament | 45.5% |
| MUNE | 36.4% |
| Which candidate would be the best predictive biomarker… 3 | |
| …in infants | |
| Neurofilament | 72.7% |
| CMAP | 63.6% |
| MUNE | 27.3% |
| …in children and teens | |
| Neurofilament | 63.6% |
| CMAP | 54.5% |
| MUNE | 27.3% |
| …in adults | |
| CMAP | 54.5% |
| Neurofilament | 36.4% |
| Blood markers of muscle damage | 36.4% |
| Which candidate would be the best prognostic biomarker… 3 | |
| …in infants | |
| Neurofilament | 72.7% |
| CMAP | 54.5% |
| SMN protein | 27.3% |
| …in children and teens | |
| Neurofilament | 63.6% |
| Survey Two | |
| CMAP | 54.5% |
| SMN protein | 36.4% |
| …in adults | |
| CMAP | 54.5% |
| Neurofilament | 45.5% |
| MUNE | 27.3% |
| What are the most pressing data gaps in our understanding of NF as a biomarker for SMA?4 | |
| Age-related changes in NF levels in healthy individuals compared to pathological disease changes | 4.67 |
| Identification of disease onset and tracking of disease progression in patients with ≥3 copies of SMN2 (i.e., understanding NF changes by SMA type) | 4.50 |
| Understanding if threshold values vs. change from baseline for an individual person is more pertinent in tracking disease progression/treatment response | 4.33 |
| Please rank the following data collections in order of highest priority to lowest priority according to which would be most helpful in advancing NF as a biomarker:5 | |
| Determination of the best assay to measure NF | 1 |
| Collection of control data in healthy older adults to understand NF during aging in order to create reference values | 2 |
| Comparison of both NF-H and NF-L in patients of different ages and disease status and the response to treatment | 3 |
| Collection of data in older teens/adults with SMA both on treatment and not on treatment to understand disease course and impacts of treatment on NF | 4 |
| Data from both SMA patients and controls to determine if threshold values or changes from baseline in individuals are better indicators of need for treatment/ treatment response | 5 |
| Collection of control data in healthy infants/ young children to understand developmental changes in NF in order to create reference values | 6 |
| Survey Three | |
| Two additional biomarker candidates, SMN protein and CMAP, were ranked highly by this Working Group. Do you favor revisiting these, or remaining focused on NF alone?6 | |
| Revisit SMN protein and CMAP | 71.4% |
| Continue with NF, not revisiting SMN and CMAP | 28.6% |
| The Working Group would like to delay revisiting SMN protein until further data (e.g., from Roche) are published. Should CMAP be assessed for adults (as NF may be less informative in older ages)? What approach would you suggest moving forward?6 | |
| Delay SMN protein assessment until further data become available while continuing with an assessment of CMAP for older patients | 50.0% |
| Do not continue with either assessment, focusing entire effort on NF | 33.3% |
| Continue with both an assessment of SMN protein and also with an assessment of CMAP for older patients | 16.7% |
| The group agrees that NF may not be as suitable in adult patients as in younger populations. What do you think is the most promising outcome or biomarker for adults?6 | |
| CMAP | 50.0% |
| Serum creatinine | 33.3% |
| SMN protein | 16.7% |
1Rankings of 1–5 (1 = least interested and 5 = most interested) were averaged to obtain group scores. 2Working Group advisors could choose more than one biomarker. 3Results represent the percentage of Working Group advisors who ranked these biomarkers among the top three candidates for stated age group and function. 4Rankings of 1–5 (1 = least pressing and 5 = most pressing) were averaged to obtain group scores. 5Rankings of 1–6 (1 = highest priority and 6 = lowest priority) were averaged to obtain group scores. 6Working Group advisors chose one biomarker.