Clinical Trials in Progressive Supranuclear Palsy

Clinical Trials in Progressive Supranuclear Palsy

Overview

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| Terminated/Withdrawn | Multiple | Important for understanding |

Active Trials

Recruiting

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

Active, Not Recruiting

NCT05222386 — Community Outreach for Palliative Engagement — PSP

• Status: Active, not recruiting
• Sponsor: University of Rochester
• Purpose: Palliative care approaches for PSP patients
• Significance: Addresses quality of life and symptomatic management

...

Clinical Trials in Progressive Supranuclear Palsy

Overview

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| Terminated/Withdrawn | Multiple | Important for understanding |

Active Trials

Recruiting

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

Active, Not Recruiting

NCT05222386 — Community Outreach for Palliative Engagement — PSP

• Status: Active, not recruiting
• Sponsor: University of Rochester
• Purpose: Palliative care approaches for PSP patients
• Significance: Addresses quality of life and symptomatic management

NCT07105384 — Quantification Tools for a Novel Tau PET Marker in PSP

• 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

Completed Trials

NCT04539041 — NIO752 (Novartis Tau ASO)

• 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](/genes/mapt) | [Tau protein](/proteins/tau)

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

NCT04608604 — Mobility in Atypical Parkinsonism: Physiotherapy Trial

• 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](/diseases/frontotemporal-lobular-degeneration)

Failed Trials (Critical Learning)

Failed trials provide essential evidence about disease mechanisms and therapeutic approaches. Documenting WHY they failed is crucial for future development.

NCT00385710 — Valproic Acid in PSP

• Status: Completed (Failed)
• Phase: Phase 2
• Sponsor: Nantes University Hospital
• Intervention: Valproic acid ([HDAC](/entities/hdac-enzymes) 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

Symptomatic Trials

Prior Approaches (Historical)

| Drug | Mechanism | Outcome |
|------|-----------|---------|
| Tetrabenazine | VMAT2 inhibitor | Variable response |
| Neflamapimod | p38 MAPK inhibitor | Mixed results |
| Typhaneoside | TCM neuroprotection | Ongoing in China |

Therapeutic Approaches Being Explored

Disease-Modifying Therapies

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

Symptomatic 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-Funded Research

CurePSP is the primary non-profit funding PSP research. Key areas:

• Natural history studies
• Biomarker development
• Clinical trial readiness
• Healthcare provider education

NINDS Natural History Studies

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

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

Related Pages

• [Progressive Supranuclear Palsy
• [Tau Protein](/proteins/tau)
• [MAPT Gene](/genes/mapt)
• [4R Tauopathies](/mechanisms/tau-pathology)
• 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.)