Table 1.
Targets and investigational therapies in FTD and related disorders
| Target | Agent | Mechanism(s) | Status | Limitations | Reference/NCT* |
|---|---|---|---|---|---|
| Tau | Lithium | GSK inhibitor | Phase 2 CBD/PSP completed | Toxicity | NCT00703677 |
| NP12 (tideglusib) | GSK inhibitor | Phase 2 AD, PSP | Toxicity | NCT01350362, NCT01049399 | |
| Riluzole | Na Channel blocker | Phase 2 PSP completed | Not efficacious | 1 | |
| Co-Q10 | Improve mitochondrial function | Phase 2 in PSP completed, Phase 3 underway | Mechanism? | 2,3 NCT00382824 | |
| rasagaline | MAO inhibitor | Phase 3 underway | Mechanism? | NCT01187888 | |
| davunetide | microtubule stabilizer | Phase 2/3 underway in PSP | Specificity | NCT01110720, NCT01056965 | |
| methylene blue | Inhibits aggregation | Completed phase 2 in AD | Mechanism? | NCT00515333 | |
| epothilones | Microtubule stabilizer | Pre-clinical | Toxicity | 4 | |
| Anti-tau mAb or vaccines | Block transmission, increase clearance | Pre-clinical | Safety? | 5–7 | |
| Hsp90 inhibitors | Increased clearance | Pre-clinical | N/A | 8 | |
| Chloroquine | Enhance autophagy | Pre-clinical | N/A | 8 | |
| RNA binding drugs, antisense oligonucleotides | Alter tau exon 10 splicing to decrease 4R, decrease tau mRNA | Pre-clinical | BBB permeability, feasibility? | 9 | |
| PGRN | Chloroquine | Increase secretion/vacuolar alkalinization | Pre-clinical, clinical trial planned | Toxicity, BBB penetration | 10 |
| Amiodarone | Increase secretion/vacuolar alkalinization | Pre-Clinical | Toxicity, mechanism | 10 | |
| SAHA | Increase PGRN expression (HDAC inhibitor) | Pre-clinical | Toxicity, BBB penetration | 11 | |
| Resveratrol | Increase PGRN expression | Pre-clinical | N/A | 11 |