Table 2.
Recent clinical trials for Parkinson’s disease involving small molecules as potential therapeutic agents that may modify disease course.
| Agents | Mechanism of Action | Phase Development | Status/Findings |
|---|---|---|---|
| Deferiprone | Iron chelator. Interferes with α-syn aggregation. | Pilot study | Improved motor scores. UPDRS. (Devos, 2014) [118]. |
| Phase 2/3 NCT00943748 |
Improved motor scores. UPDRS. (Grolez, 2015) [119] |
||
| Phase 2 NCT01539837 |
Improvement trend in motor scores. (Martin-Bastida, 2017) [120] |
||
| Phase 3 NCT02655315 |
Therapy leads to PD worsening. (Devos, NEJM, 2022) [121] |
||
| Squalamine phosphate/ENT-01 | Interferes with α-syn aggregation by displacing α-syn from membranes. | Phase 2 NCT03047629 |
Improvement in constipation. (Hauser, 2019) [122] |
| Phase 2b NCT03781791 |
Safe. Improvement in constipation. (Camilleri, 2022) [123] |
||
| Buntanetap/Posiphen (ANVS 401) | Reduces α-syn protein translation | Phase 3 NCT05357989 |
Improvement in motor, nonmotor, cognitive symptoms. (Annovis Bio, New release, 2024) [124] |
| Anle 138b | Inhibits α-syn oligomer formation | Phase 1 NCT04208152 |
In healthy volunteers excellent safety, tolerability at all dose-plasma levels [125] |
| Phase 2 NCT04685265 |
Good safety, tolerability confirmed in PD patients (Levin, 2023; Mov Disord) [125] |
||
| Nilotinib | c-Abl inhibitor enhances autophagic clearance of α-syn | Phase 2 NCT03205488 |
Acceptable safety/tolerab. Low brain penetration. No biomarkers effect. No efficacy. (Simuni, 2021, JAMA Neurol) [126] |
| YTX-7739 | Inhibits stearoyl-CoA desaturase, promotes smaller α-syn aggregates | Phase 1b Trial NL 9172 |
Well tolerated in PD patients. Mild/moderate adverse events (Press Release, 2021, NL) [127] |
| NPT200-11 | Interferes with α-syn aggregation, displacing α-syn from membranes | Phase 1 NCT02606682 |
In healthy volunteers Data not published. (Journal of Parkinson’s Disease 13; 4:2023) [128] |