Table 1.
Preclinical studies on trampirosate.
| Study | Model | Treatments | Outcomes |
|---|---|---|---|
| Gervais et al. (10) | TgCRND8 mice* | 30 or 100 mg/kg tramiprosate daily (s.c.) during 8–9 weeks.Controls were treated with sterile water. | Significant reduction in amyloid plaque in the brain. Significant decrease in the cerebral levels of soluble and insoluble Aβ40 and Aβ42. Dose-dependent reduction of plasma Aβ. |
| Galarneau et al. (35) | Rat primary neurons (in vitro) | Tramiprosate.3-H muscimol (control). | Tramiprosate bound to the GABA-AR with high affinity. Tramiprosate and 3-H muscimol induced a dose-dependent membrane depolarization and calcium flux. Tramiprosate and 3-H muscimol decreased basal and Aβ42-induced caspase 3/7 activity. |
| Azzi et al. (34) | Primary neurons and OHC (in vitro) | Tramiprosate.Muscimol (control). | Tramiprosate decreased basal and Aβ42-induced caspase 3/7 and caspase 9 activities. Decreased Aβ42-induced cellular mortality in OHC. |
| Krzywkowski et al. (39) | Rat hippocampal neurons (in vitro) | Tramiprosate | Tramiprosate prevented Aβ-induced inhibition of LTP. |
| Greenberg et al. (40) | Rat primary cortical/hippocampal neurons (in vitro) | TramiprosateMuscimol (control) | Tramiprosate inhibited Aβ42-induced ERK1/2 activation by a GABA-A-independent mechanism. |
| Santa-Maria et al. (38) | HEK293 tau cells (in vitro) SH-SY5Y cells (in vitro) | Tramiprosate, 3-APS, Alzhemed™ | 3-APS promoted abnormal aggregation of tau 3-APS did not affect the binding of tau to microtubules |
3-APS, 3-amino-1-propane sulfonic acid; ERK1/2, extracellular signal-regulated protein kinases 1 and 2; GABA-AR, γ-amino butyric acid A receptor; HEK, human embryonic kidney cells; LTP, long term potentiation; OHC, organotypic hippocampal slice cultures; s.c., subcutaneous; SH-SY5Y, human neuroblastoma cell line.
*Alzheimer's disease model. Transgenic mice overexpressing mutant human APP at levels approximately 5-fold higher than endogenous murine APP.