This page tracks all clinical trials for Progressive Supranuclear Palsy (PSP), a primary 4R-tauopathy. PSP has historically been challenging to treat due to limited understanding of disease mechanisms and difficulties in patient recruitment due to disease rarity. The therapeutic pipeline remains small compared to Alzheimer's Disease or Parkinson's Disease, but several approaches are being explored.
¶ Current Trial Landscape
| Status |
Count |
Notes |
| Recruiting |
1 |
First-in-human tau ligand |
| Active, Not Recruiting |
2 |
Imaging biomarkers, palliative care |
| Completed |
6+ |
Includes failed and successful |
| Terminated/Withdrawn |
Multiple |
Important for understanding |
¶ NCT07348276 — First-in-Human Study for Safety and Evaluation of Two 4R Tau Ligands in PSP
- Status: Recruiting
- Phase: Early Phase 1
- Sponsor: Invicro
- Intervention: Two novel 4R tau PET ligands
- Purpose: First-in-human evaluation of tau tracer specificity for PSP
- Significance: Improved tau imaging could enable better diagnosis and trial enrollment
- Status: Active, not recruiting
- Sponsor: University of Rochester
- Purpose: Palliative care approaches for PSP patients
- Significance: Addresses quality of life and symptomatic management
- Status: Active, not recruiting
- Phase: Phase 2
- Sponsor: Fundacion Clinic per a la Recerca Biomédica
- Intervention: [18F]PI-2620 PET imaging
- Purpose: Validate tau PET quantification in PSP
- Status: Completed
- Phase: Phase 1
- Sponsor: Novartis Pharmaceuticals
- Intervention: NIO752 — antisense oligonucleotide targeting MAPT mRNA
- Mechanism: 4R tau reduction via RNA interference
- Results: Safety established; efficacy data pending publication
- Significance: First antisense approach for 4R tauopathies; similar to tofersen (SOD1) but targeting tau
- Related: MAPT gene | Tau protein
¶ NCT04715750 — [18F]PI-2620 PET in AD and PSP
- Status: Completed
- Phase: Phase 1
- Sponsor: Life Molecular Imaging GmbH
- Purpose: Imaging biomarker development for tau in PSP
- Results: PI-2620 shows binding in PSP tauopathy regions
- Status: Completed
- Intervention: Physiotherapy
- Sponsor: Victoria Sidoroff
- Purpose: Evaluate rehabilitation approaches
¶ NCT02365922 — ARTFL (Advancing Research and Treatment for Frontotemporal Lobar Degeneration)
- Status: Completed
- Type: Observational
- Sponsor: University of California, San Francisco
- Purpose: Natural history study for FTLD including PSP
- Related: FTLD
Failed trials provide essential evidence about disease mechanisms and therapeutic approaches. Documenting WHY they failed is crucial for future development.
- Status: Completed (Failed)
- Phase: Phase 2
- Sponsor: Nantes University Hospital
- Intervention: Valproic acid (HDAC inhibitor)
- Rationale: Histone deacetylase inhibition might modulate tau pathology
- Outcome: No significant benefit over placebo
- Failure Analysis:
- Insufficient target engagement at tested doses
- Possible that HDAC inhibition is not the right mechanism
- Need for better biomarkers to demonstrate target engagement
- Lessons Learned:
- HDAC inhibition alone may not be sufficient for PSP
- Combination approaches may be needed
- Biomarker-driven patient selection could improve outcomes
| Drug |
Mechanism |
Outcome |
| Tetrabenazine |
VMAT2 inhibitor |
Variable response |
| Neflamapimod |
p38 MAPK inhibitor |
Mixed results |
| Typhaneoside |
TCM neuroprotection |
Ongoing in China |
-
Anti-tau therapies
- ASOs (NIO752)
- Tau aggregation inhibitors
- Tau phosphorylation modulators
-
Tau imaging biomarkers
- [18F]PI-2620
- Novel 4R-selective ligands
-
Neuroprotection
- p38 MAPK inhibitors
- Anti-inflammatory approaches
-
Movement disorder management
- Balance and gait training
- Fall prevention
- Assistive devices
-
Oculomotor dysfunction
- Prismatic glasses
- Eye movement training
-
Dysphagia management
- Swallowing therapy
- Nutritional support
-
Cognitive/behavioral
- Standard approaches for dementia
CurePSP is the primary non-profit funding PSP research. Key areas:
- Natural history studies
- Biomarker development
- Clinical trial readiness
- Healthcare provider education
The National Institute of Neurological Disorders and Stroke supports:
- PSP biomarker studies
- Clinical rating scale validation
- Patient registry development
¶ Research Gaps and Opportunities
- No approved disease-modifying therapies — Major unmet need
- Small patient population — Challenges for trial recruitment
- Biomarker development — Critical for patient selection and endpoint validation
- Genetic forms — PSP cases with MAPT mutations could inform therapeutic development
- Combination therapy — Likely needed for multifactorial pathology
- [Progressive Supranuclear Palsy
- Tau Protein
- MAPT Gene
- 4R Tauopathies
- Clinical Trials Dashboard
- Neflamapimod PSP Trial
- Tetrabenazine PSP Trial
- Typhaneoside PSP Trial](/diseases/amyotrophic-lateral-sclerosis)## References
- Unknown, ClinicalTrials.gov: PSP Trials (n.d.)
- Unknown, CurePSP Research Directory (n.d.)
- Unknown, NINDS PSP Information (n.d.)