Type: Clinical outcome measure (clinician-rated)
Purpose: Quantify disease severity in Progressive Supranuclear Palsy (PSP)
Developer: Dr. Lawrence I. Golbe and colleagues
Original publication: 2004[@golbe2004]
Current use: Primary endpoint in FNP-223 PROSPER trial, LY-3372689 LOTUS trial, and most PSP therapeutic trials
Overview
flowchart TD
PSP["PSP"] -->|"associated with"| Alzheimer["Alzheimer"]
PSP["PSP"] -->|"associated with"| Als["Als"]
PSP["PSP"] -->|"associated with"| Alzheimer_s_disease["Alzheimer's disease"]
PSP["PSP"] -->|"expressed in"| neurons["neurons"]
PSP["PSP"] -->|"downregulates"| SV2A["SV2A"]
PSP["PSP"] -->|"targets"| tauopathy["tauopathy"]
PSP["PSP"] -->|"participates in"| unfolded_protein_response["unfolded protein response"]
PSP["PSP"] -->|"regulates"| STX6["STX6"]
PSP["PSP"] -->|"associated with"| frontotemporal_dementia["frontotemporal dementia"]
PSP["PSP"] -->|"participates in"| oxidative_stress_response["oxidative stress response"]
PSP["PSP"] -->|"associated with"| Parkinson_s_disease["Parkinson's disease"]
PSP["PSP"] -->|"regulates"| Parkinson_s_disease["Parkinson's disease"]
PSP["PSP"] -->|"associated with"| tauopathy["tauopathy"]
PSP["PSP"] -->|"biomarker for"| Ms["Ms"]
style PSP fill:#4fc3f7,stroke:#333,color:#000
...Type: Clinical outcome measure (clinician-rated)
Purpose: Quantify disease severity in Progressive Supranuclear Palsy (PSP)
Developer: Dr. Lawrence I. Golbe and colleagues
Original publication: 2004[@golbe2004]
Current use: Primary endpoint in FNP-223 PROSPER trial, LY-3372689 LOTUS trial, and most PSP therapeutic trials
Overview
Mermaid diagram (expand to render)
The PSP Rating Scale (PSPRS) is a 0-100 point clinician-administered scale specifically designed for PSP. It assesses six domains of neurological function: daily activities (DAS), behavior (Beh), bulbar (Bul), ocular motor (OM), gait/mobility (Gait), and axial (Ax). The scale has become the standard primary endpoint for PSP clinical trials["@psprs"].
Scale Structure
The PSPRS contains 28 items across six domains[@psprs][@cook2023]:
Domain Breakdown
| Domain | Abbrev | Max Points | Items | Content |
|--------|--------|------------|-------|---------|
| Daily Activities | DAS | 28 | 7 | Dressing, hygiene, feeding, walking, choking, cutting food, |
| Behavior | Beh | 3 | 1 | Neuropsychiatric features |
| Bulbar | Bul | 9 | 6 | Speech, swallowing, eye movements, handwriting |
| Ocular Motor | OM | 16 | 4 | Vertical gaze, horizontal gaze, convergence, eyelid |
| Gait/Mobility | Gait | 12 | 4 | Standing, initiation of gait, walking, falls |
| Axial | Ax | 8 | 2 | Posture, rising from chair |
Total maximum: 100 points (higher = more severe)
Key Features
- Trained examiner required — Standardized administration by trained neurologists
- Takes 20-30 minutes to complete
- Interview + exam — Combines patient/caregiver history with direct examination
- Published anchor-based MCID: 4-6 points (minimally clinically important difference)
Scoring Interpretation
| PSPRS Score | Disease Severity | Clinical Context |
|-------------|-----------------|------------------|
| 0 | No impairment | Healthy |
| 1-20 | Early PSP | Often still independent |
| 21-40 | Moderate PSP | Progressive functional decline |
| 41-60 | Advanced PSP | Significant disability, wheelchair common |
| 61-80 | Late PSP | Bedridden, feeding tube often needed |
| 81-100 | End-stage PSP | Severe disability, hospice care |
Rate of progression: Untreated PSP patients typically decline 8-12 PSPRS points per year.
Use in Clinical Trials
As Primary Endpoint
PSPRS is the established primary endpoint for PSP therapeutic trials because:
Disease-specific: Designed for PSP, unlike generic dementia scales (MMSE, ADAS-Cog)
Sensitive to change: Detects meaningful decline over 12-18 months
Clinically meaningful: Scores correlate with functional status and caregiver burden
Regulatory acceptance: Accepted by FDA and EMA as primary endpoint for PSP trialsIn OGA Inhibitor Trials
FNP-223 PROSPER Trial (NCT06355531):
- Primary endpoint: Change from baseline in PSPRS at 52 weeks
- Secondary endpoints: Other clinical measures, biomarker endpoints
LY-3372689 LOTUS Trial (NCT05682807):
- Primary endpoint: Change from baseline in PSPRS at 52 weeks
- Provides head-to-head comparison with PROSPER for FNP-223
Challenges in Trial Use
- Inter-rater variability: Requires rigorous site training and certification
- Learning effects: Patients/families may anticipate questions
- Floor/ceiling effects: Less useful for very early or very advanced PSP
- Missing data: Patient dropout due to disease progression
Development and Validation
Original Development
Developed by Golbe et al. (2004) through:
- Literature review of existing scales
- Expert panel consensus (movement disorder neurologists)
- Field testing in 100+ PSP patients
- Rasch analysis for item performance[@psprs]
Validation Studies
- Reliability: Inter-rater ICC > 0.90 with training
- Construct validity: Correlates with disease duration, functional scales
- Responsiveness: Sensitive to change over 6-12 months
- Cross-cultural: Validated in multiple languages
Updated Considerations (2023+)
Recent work by Cook et al. addresses contemporary trial design[@cook2023]:
- Digital PSPRS administration for improved reliability
- Remote assessment options for expanded trial access
- Composite endpoints incorporating PSPRS plus cognitive measures
Cross-Links
- [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-psp) — Disease measured by PSPRS
- [FNP-223 PROSPER Trial](/clinical-trials/fnp223-prosper-phase2-psp) — Trial using PSPRS as primary endpoint
- [LY3372689 LOTUS Trial](/clinical-trials/ly3372689-lotus-phase2-psp) — Competitive PSP trial
- [Dr. Marcus Cook](/researchers/marcus-cook) — PSPRS endpoint optimization researcher
References
[Golbe et al., A rating scale for progressive supranuclear palsy (Neurology, 2004)](https://pubmed.ncbi.nlm.nih.gov/15277622/)
[Cook et al., Clinical outcome assessment in PSP trials (Mov. Disord., 2023)](https://pubmed.ncbi.nlm.nih.gov/37400002/)Pathway Diagram
The following diagram shows the key molecular relationships involving PSP Rating Scale (PSPRS) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)