Table 2.
Longitudinal “wet biomarker” studies in ALS.
| Author(s) and year of publication | Follow-up interval (months) | Number of patients / number of controls | Candidate biomarker evaluated | Biofluid | Assessment method used | Summary of conclusion |
|---|---|---|---|---|---|---|
| *Okada et al. (150) | 12 | 57/0 | creatinine | serum | NA | -progression detected (creatinine) |
| Raheja et al. (151) | NA | NA | microRNAs | serum | NA | - progression detected (miR-136-3p, miR-30b-5p, miR-331-3p, miR-496, miR-2110) |
| Thompson et al. (152) | 30 | 49/52 | chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), and chitinase-3-like protein 2 (CHI3L2), (phosphorylated neurofilament heavy chain) Pnfh | CSF | nano ultra-high performance liquid chromatography tandem mass spectrometry (nUHPLC LC-MS/MS), ELISA | - progression detected (CHI3L1) |
| Di Pietro et al. (153) | NA | 14/24 | micro-RNAs- MIR206, MIR208B, MIR499 | skeletal muscle | quantitative real time PCR, Western blot analysis | - progression detected (MIR208B, MIR499, MIR206, HDAC4) |
| Murdock et al. (154) | Every 6–12 months | 119/35 | leukocytes | blood | flow cytometry | - progression detected (immune cells), associated with ALSFRS-R |
| Shepheard et al. (155) | NA | 54/45 | urinary p75ECD | urine | sandwich ELISA | - progression detected (urinary p75ECD), correlated with ALSFRS-R |
| van Ejik et al. (156) | NA | 1241/0 | creatinine | plasma | NA | - progression detected (plasma creatinine), correlated to ALSFRS-R, muscle strength, mortality |
| Waller et al. (157) | 3 | 22/0 | microRNAs, miR-17-5p, miR-223-3p, miR-24 | serum | Qiagen miScript-based Qpcr | - progression detected (mir-206, mir-143-3p, mir-374b-5p) |
| McCombe et al. (158) | 27 | 98/61 | pNFH | serum | NA | - progression detected (pNFH) |
| Lu et al. (159) | 36 | 136/104 | neurofilament heavy chain-phosphoform | plasma | ELISA | - progression detected (NfH) |
| *Levine et al. (160) | 6 | 28/0 | tau, pNFH | CSF | ELISA | - progression detected (tau) |
| *Levine et al. (161) | 12 | 20/0 | tau, pNFH | CSF | ELISA | - progression detected (tau) |
| Wilson et al. (162) | 24 | 44/60 | cystatin C | CSF, plasma | quantitative enzyme linked immunosorbent assay (ELISA) | - progression detected (cystatin C) |
| Gaiani et al. (163) | 36 | 94/82 | ALSFRS-R, NFL | CSF | enzyme-linked immunosorbent assay (UmanDiagnostics AB) | - NFL may have role as a biomarker |
| Lu et al. (164) | 48 | 95/88 | CK, ferritin, tumor necrosis factor (TNF)–a, and interleukin (IL)−1b, IL-2, IL-8, IL-12p70, IL-4, IL-5, IL-10, and IL-13, IL-6, IFN-Y | plasma | multiplex electrochemiluminescence immunoassay | - no defined progression |
| Steinacker et al. (165) | 24 | 125/28 | neurofilament light chain (NF-L), progranulin (PGRN), S100 | serum, CSF (baseline only) | ELISA, electrochemiluminescence (ECL) immunoassay, ECLIA Elecsys (Roche, Penzberg, Germany) | - no progression reported |
| Gibson et al. (166) | 12 | 80/0 | CK | NA | NA | - no progression detected |
| Gray et al. (167) | 24 | 41/14 | CSF- glucose, lactate, citric acid, ethanol | CSF | H-NMR | - no progression reported |
| Lu et al. (168) | 36 | 167/78 | neurofilament light chain (NFL) | serum, blood, CSF | electrochemiluminescence immunoassay | - no progression detected |
| Verstraete et al. (169) | NA | 219/100 | TDP-43 | plasma | sandwich ELISA | - no defined progression |
| Nardo et al. (170) | 6 | 94/64 | PRDX2, GSTO1, CLIC1, HSC70, CypA, PDI, ERp57, CALR, PA28a, IRAK4, FUBP1, ROA2, actinNT, TDP-43 | blood PBMC | 2D-DIGE, mass spectometry | - no progression reported |
*
indicates clinical trial.