Table 1:
Mechanistic Based Trials for PSP
| Pathogenic Mechanism | Therapeutic Mechanism | Drug Name | Trials/References | Phase | Main Outcomes | Results | Ongoing |
|---|---|---|---|---|---|---|---|
| Inflammation | Anti-inflammatory/antioxidants | CoQ10 | [93] [94] | II, II | PSP-RS, ADL, MMSE, PDQ-39 | No benefit | Completed |
| Riluzole | [95] | III | Survival, H/Y, SEADL, MMSE | No benefit | Completed | ||
| Rasagiline | [96] | II | PSP-RS | No benefit | Completed | ||
| Lipid Peroxidation | Lipid Stabilization | RT-001 | [203] | Pre-Clinical | |||
| Tau | GSK-3β Inhibitors | Valproic Acid | NCT00385710 | II | PSP-RS | No benefit | Completed |
| Phosphorylation | [196] | ||||||
| Lithium | NCT00703677 | I (PSP) | Tolerability, PSP-RS, PSP-QOL | Not tolerated | Completed | ||
| No benefit | |||||||
| Tideglusib | NCT01350362 | II | PSP-RS, DRS, SEADL, | No benefit | Completed | ||
| [197] [198] | EuroQol | ||||||
| CDK5 inhibitors | Tolfenamic Acid | NCT04253132 | IIa | Tolerability | Not yet recruiting | ||
| Tau Acetylation | Acetylation Inhibitors | Salsalate | NCT02422485 | I | Tolerability, PSP-RS | Not posted | Active, not recruiting |
| O-GlcNAc | O-GlcNAc Inhibitors | [200] [201] | Pre-clinical | ||||
| Tau Assembly | Microtubule Stabilizing Agents | Davunetide | NCT01056965 | II/III | PSP-RS, SEADL, RBANS | No benefit | Completed |
| [205] | |||||||
| TPI-287 | NCT02133846 | I | Tolerability | Not tolerated | Active not recruiting | ||
| [207] | |||||||
| Epothilone D | [208] | Pre-clinical | |||||
| Tau | Passive | ABBV-8E12 | NCT02985879 | II | PSP-RS, Tolerability | No benefit | Completed |
| Accumulation/Spread | Immunotherapy | NCT03391765 | II Extension | PSP-RS | No benefit | Completed | |
| BIIB092 | NCT03068468 | II | PSP-RS, Tolerability | No benefit | Completed | ||
| [224] | |||||||
| UCB0107 | NCT04185415 | Ib | Tolerability | Recruiting | |||
| Active Immunotherapy | No agents in PSP | ||||||
| Tau Production | ASO | [251] | Pre-clinical | ||||
| siRNA | [251] | Pre-clinical | |||||
| Neurotrophic | Neurotrophic Inducer | AZP2006 | NCT04008355 | II | Not yet recruiting | ||
| Inducer | |||||||
Abbreviations: PSP-RS: Progressive Supranuclear Palsy Rating Scale, ADL: activities of daily living, MMSE: minimental status exam, PDQ-39: Parkinson's disease questionnaire-39, H/Y: Hoehn and Yahr scale, SEADL: Schwab and England activities of daily living, PSPQOL: PSP quality of life scale, EuroQol: European quality of life scale, RBANS: repeatable battery for the assessment of neuropsychological status, ASO: antisense oligonucleotides, siRNA: small interfering RNA.