Table 2.
Tau-directed therapeutics tested in clinical trials.
| Therapeutic | Synonyms | Mechanism | Rationale (Ref #) |
Preclinical Data (Ref #) |
Furthest Development Phase |
|---|---|---|---|---|---|
| GENE EXPRESSION | |||||
| BIIB080 | IONIS-MAPTRx, ISIS 814907 | ASO targeting decreased total tau expression | 12, 31, 34 | 37 | AD (Phase 2) |
| KINASE INHIBITOR | |||||
| Lithium | GSK-3β inhibitor | 44, 45 | 46 | AD (Phase 2 - D/C), PSP (Phase 2- D/C), CBS (Phase 2- D/C), MCI (Phase 2), BvFTD (Phase 2) | |
| Valproate | Depakote, divalproex, valproic acid | GSK-3β inhibitor | 48 | 49 | AD (Phase 3 - D/C), PSP (Phase 2 - D/C) |
| Tideglusib | NP031112, Nypta, Zentylor, NP12 | GSK-3β inhibitor | 53 | 54 | AD (Phase 2 - D/C), PSP (Phase 2 - D/C) |
| Saracatinib | AZD0530 | Fyn inhibitor | 59, 60 | 61 | AD (Phase 2) |
| Nilotinib | Tasigna, AMN107 | Abl inhibitor | 64 | 65 | AD (Phase 2) |
| OGA INHIBITOR | |||||
| MK-8719 | O-GlcNAcase inhibitor | 66 | 67 | Healthy Controls (Phase 1 – D/C) | |
| ASN120290 | ASN-561 | O-GlcNAcase inhibitor | 66 | 69 | Healthy Controls (Phase 1) |
| ACETYLATION INHIBITOR | |||||
| Salsalate | Tau acetylation inhibitor | 28, 29 | 71 | AD (Phase 2) PSP (Phase 2 – D/C) | |
| TAU AGGREGATION INHIBITOR | |||||
| Rember TM | Methylene Blue, methylthioninium (MT), TRx-0014 | Tau aggregation inhibitor (TAI) | 74 | 75, 76 | AD (Phase 2 - D/C) |
| LMTM | TRx0237, LMT-X | Tau aggregation inhibitor (TAI) | 74 | 79 | AD (Phase 3), BvFTD (Phase 3 – D/C) |
| ACTIVE IMMUNIZATION (VACCINATION) | |||||
| AADvac-1 | Tau fragment of MTBR conjugated to keyhole limpet hemocyanin | 92, 94 | 94 | AD (Phase 2), NfvPPA (Phase 2) | |
| ACI-35 | Ptau fragment anchored on liposome | – | 97 | AD (Phase 2) | |
| PASSIVE IMMUNIZATION (ANTIBODY TRANSFUSION) | |||||
| RG7345 | RO6926496 | mAb to tau pS422 near C-terminal | 101 | 102 | Healthy Controls (Phase 1 - D/C) |
| BIIB092 | BMS-986168, IPN007 | mAb to tau N-terminal (aa 15-24) | 85, 99 | 99 | PSP (Phase 2 – D/C), AD (Phase 2), Tauopathies (Phase 2 – D/C) |
| C2N 8E12 | ABBV-8E12 | mAb to tau N-terminal (aa 25-30) | 85 | 105-107 | PSP (Phase 2 – D/C), AD (Phase 2) |
| RO7,105,705 | Semorinemab, RG 6100 | mAb to tau N-terminal (reduced effector function) | 85, 109 | 109 | AD (Phase 2) |
| LY3303560 | Zagotenemab | mAb to tau N-terminal (tau aggregates) | 85 | 110 | AD (Phase 2) |
| BIIB076 | NI-105, 6C5 huIgG1/λ | mAb to “pan-tau” (monomers and fibrils) | – | 111 | AD (Phase 2) |
| UCB0107 | UCB 0107 | mAb to tau mid domain (aa 235-246) | – | – | Healthy Controls (Phase 1) |
| JNJ-63733657 | mAb to tau mid domain | – | – | AD (Phase 2) | |
| MICROTUBULE STABILIZATION | |||||
| Davunetide | NAP, AL-108 | Growth factor derived neuropeptide | 114 | 115, 116 | MCI (Phase 2 - D/C), PSP (Phase 3 - D/C), Tauopathies (Phase 2 - D/C) |
| Epothilone D | BMS-241027 | Taxane derivitive that stabilizes microtubules | – | 120 | AD (Phase 2 - D/C) |
| TPI 287 | Taxane derivitive that stabilizes microtubules | 122 | – | AD (Phase 2 – D/C), CBS (Phase 2 – D/C), PSP (Phase 2 – D/C) | |