Table 5.
Small molecules attenuating Aβ-induced neurotoxicity
| Name (Alternative name) |
Mechanism of action | Clinical phase (Current status) |
Pathological biomarker | Cognition | Ref |
|---|---|---|---|---|---|
| Synaptotoxicity modulators | |||||
| Zervimesine (CT1812, Elayta) | TMEM97 modulator | Phase 2 (START, ongoing) |
*CSF proteomics: synapse- and inflammation-related proteins normalized *CSF NfL ↓ (300 mg) *CSF Aβ42 ↓ (300 mg) |
No benefit overall; Low p-tau217 subgroup ↑ (ADAS-Cog11) | [145, 147-150] |
| Simufilam (PTI-125) | Filamin A modulator (disrupts Aβ-α7nAChR interaction) | Phase 3 (ReThink-ALZ, completed) Phase 3 (ReFocus-ALZ, terminated for sponsor decision) |
No benefit | No benefit | [152] |
| ALX-001 (BMS-984923) | mGluR5 SAM | Phase 1b (ongoing) | No data available | No data available | [156] |
| Hyperexcitability modulators | |||||
| Levetiracetam | SV2A modulator | Phase 2/3 (HOPE4MCI-AGB101, completed) | No data available | No benefit | [157] |
*Asterisks indicate statistically significant differences. Arrows indicate the direction of change: for cognitive outcomes, ↑ and ↓ represent improvement or worsening, respectively; for pathological biomarkers, ↑ and ↓ indicate numerical increase or decrease. (-) indicates no change.