This first-in-human study evaluates two novel 4R tau-selective PET ligands specifically designed for imaging 4-repeat tauopathies including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), and Argyrophilic Grain Disease (AGD).
The study represents a critical advance in neuroimaging for tauopathies, addressing the fundamental limitation of existing tau PET tracers that show suboptimal binding to 4R tau isoforms predominant in PSP and related disorders.
| Parameter | Value |
|---|---|
| NCT Number | NCT07348276 |
| Status | Recruiting |
| Phase | Early Phase 1 |
| Sponsor | Invicro |
| Intervention | Two novel 4R tau PET ligands |
| Purpose | First-in-human safety and evaluation |
| Study Type | Interventional |
| Allocation | Non-randomized |
The tau protein is encoded by the MAPT gene and exists in six isoforms in the human brain, generated by alternative splicing. These isoforms differ in the presence of three or four microtubule-binding repeat domains:
The selective binding to 4R tau requires ligands with specific structural properties that recognize the additional microtubule-binding repeat domain present in 4R but not 3R isoforms.
4R tauopathies are a group of neurodegenerative disorders characterized by accumulation of 4R tau in the brain:
The novel 4R tau ligands are designed to:
Key properties required for an effective 4R tau PET ligand:
Current tau PET tracers have limitations when applied to PSP:
4R-selective ligands could provide:
The trial follows a traditional first-in-human design:
The study evaluates two distinct 4R tau ligand candidates, allowing direct comparison of imaging characteristics and enabling selection of the lead compound for further development.
Standard PET imaging protocol includes:
This trial represents an important step toward:
The ability to specifically image 4R tau pathology in vivo has been a long-standing goal in neurodegenerative disease research. Current diagnostic criteria for PSP and CBD rely heavily on clinical presentation, which can be variable and overlap with other disorders. A validated 4R tau PET ligand would provide objective evidence of underlying pathology, enabling earlier and more accurate diagnosis.
| Compound | Developer | Target | Status |
|---|---|---|---|
| PI-2620 | Life Molecular Imaging | 3R/4R tau | Phase 2 |
| PM-PBB3 | Aprinoia | 3R/4R tau | Phase 2 |
| [18F]RO948 | Roche | 3R/4R tau | Phase 1 |
| Flortaucipir (AV-1451) | Avid/Eli Lilly | 3R/4R tau | Approved for AD |