Table 1.
Summary of the studies presented in this review.
| Author, Year | Patient Cohorts | Treatment | Samples | Methods | Major Findings | Molecular Pathways |
|---|---|---|---|---|---|---|
| Finkel et al., 2012 [28] |
108 children with SMA (type 1–3, age 2–12 years old) and 22 controls of similar age | No treatment | Plasma | Proteomics: multidimensional liquid chromatography and eight-plex iTRAQ labels with mass spectrometry. Metabolomics: QStar Elite quadrupole time-of-flight instrument. |
Dipeptidyl Peptidase IV osteopontin, and tetranectin positively correlate with MHFMS; Fetuin-A and Vitronectin negatively correlate with MHFMS. | Dipeptidyl peptidase IV: glucose/insulin metabolism, immune response. Osteopontin: bone metabolism, immune response. Tetranectin: bone metabolism. Fetuin-A |
| Kessler et al., 2020 [29] |
SMA type 3 (n = 9); SMA type 2 (n = 1) and age- and gender-matched controls (n = 10) | Baseline and after nusinersen treatment | CSF | Proteomics: Thermo Scientific QExactive HF-X mass spectrometer | Increased PARK7/DJ-1 in the CSF; two gene expression clusters in SMA patients based on age and two gene expression clusters in SMA patients based on treatment response. No significant single protein shift after therapy. |
PARK7/DJ-1: DJ-1 acts as a chaperone and sensor under oxidative stress, protecting neurons by inhibiting α-synuclein aggregation. |
| Bianchi et al., 2021 [30] |
SMA type 1 infants (n = 10) compared with age-matched controls (n = 10) |
Baseline and after nusinersen treatment | CSF | Proteomics: SDS-PAGE followed by MALDI-TOF MS analysis |
Increased levels of APOA1, APOE, and TTR after treatment. | APOA1: the primary apolipoprotein found in high-density lipoproteins (HDLs). APOE: protein linked to neurological and neurodegenerative diseases, with lipid transport, gene polymorphisms, and expression regulation being key factors. TTR: transport protein carrying thyroid hormone and vitamin A-bound retinol, with potential roles in neuroprotection and neurite outgrowth, mutations cause amyloidosis. |
| Schorling et al., 2022 [31] |
SMA types 1, 2, and 3 (n = 3 mass spectrometry, validation n = 31) | Baseline and after nusinersen treatment | CSF | Mass spectroscopy | Cathepsin D decreased in SMA patients aged ≥2 months at the start of treatment but was only significant in patients who demonstrated a positive motor response. | Cathepsin D is a type of aspartyl protease prominently found in the central nervous system and skeletal and cardiac muscle. Its primary function is to catalyze the degradation of proteins within lysosomes. |
| Deutsch et al., 2021 [32] |
SMA pediatric (type 1–3; n = 25) and matching controls (n = 25 serum, CSF) or n = 125 (urine]) | Baseline and after nusinersen treatment | Urine, serum, and CSF | Metabolomics: 600 MHz 1H-NMR spectrometer | No metabolome shift after therapy. Creatinine urinary level reduced in SMA patients. | |
| Errico et al., 2022 [33] |
SMA pediatric patients (all three types, n = 27); no control group | Baseline and after nusinersen treatment | CSF | Metabolomics: 600 MHz 1H-NMR spectrometer | Effects after nusinersen treatment: increased metabolic rate of glucose (SMA type 1), increased ketone levels (SMA type 2), increased amino acid metabolism (SMA type 3). |