Table 1.
Potential biomarkers in spinal muscular atrophy.
| Potential Biomarker | Pros | Cons |
|---|---|---|
| Instrumental | ||
| CMAP and MUNE | ||
| • Both measures are related to phenotypic severity | • MUNE does not appear related to motor function in a group of type II patients | |
| • Progressively decrease over time (MUNE is more stable in type III) | • There is no evidence yet of correlations between motor function and CMAP variations | |
| • Are related to SMN2 copy number | ||
| • Have been evaluated in an open phase II trial of valproic acid | ||
| • CMAP, but not MUNE, increases with VPA | ||
| DXA | ||
| • Bone density increased after VPA treatment | • The biological significance of BMD reduction in SMA patients is not established | |
| • It is not known whether BMD variations are related to the clinical outcome of treatment | ||
| Molecular | ||
| SMN protein quantification | ||
| • SMN protein levels, as determined by cell immunoassay, are related to SMN2 copy number | • SMN protein levels are not related to clinical severity | |
| • For cell immunoassay, small amount of PBMC are sufficient for SMN quantification | • No stabilization buffers are commercially available for total proteins | |
| • ELISA assay is sensitive down to magnitude of pg/mL of SMN protein | • PBMC should be manipulated within 2 hours from sampling | |
| • The minimum amount of peripheral blood necessary for SMN quantification is not known | ||
| • It is not indicated for evaluation of candidate compounds which do not modify SMN levels | ||
| SMN transcript quantification | ||
| • Small amounts of blood (2.5 mL or less) are sufficient for mRNA quantification | • It is not known if protein and transcript levels are related | |
| • Several stabilization buffers are available for multicenter clinical trials | • It is unknown if transcript level variations are related to the clinical outcome of treatment | |
| • SMN transcripts are stable over time | • It is unknown if transcript levels in blood and target tissues are related | |
| • It is not indicated for the evaluation of candidate compounds which do not modify SMN levels |