Table 1.
Disease modifying agents for the treatment of Alzheimer’s disease in clinical trials.
| Disease Modifying Agents | Mechanism of Action |
|---|---|
| Phase 3 Clinical Trials | |
| Aducanumab | Monoclonal antibody—targets β-amyloid and removes it. |
| Gantenerumab | Monoclonal antibody—binds and removes β-amyloid. |
| CAD106b | Amyloid vaccine—stimulates production of antibodies against β-amyloid. |
| BAN2401 | Monoclonal antibody—reduces protofibrillar β-amyloid. |
| TRx0237 (LMTX) | Tau protein aggregation inhibitor. |
| AGB101 | Low-dose levetiracetam—improves synaptic function and reduces amyloid-induced neuronal hyperactivity |
| ALZT-OP1 (cromolyn + ibuprofen) | Mast cell stabilizer and anti-inflammatory—promotes microglial clearance of amyloid |
| Azeliragon | RAGE (Receptor for Advanced Glycation End-products) antagonist—reduces inflammation and amyloid transport into the brain |
| BHV4157 (troriluzole) | Glutamate modulator—reduces synaptic levels of glutamate and improves synaptic functioning |
| Masitinib | Tyrosine kinase inhibitor—modulates inflammatory mast cell and reduces amyloid protein and tau phosphorylation |
| Phase 2 Clinical Trials | |
| Crenezumab | Monoclonal antibody—targets soluble oligomers and removes β-amyloid |
| ABBV-8E12 | Monoclonal antibody—prevents tau propagation |
| ABvac40 | Active immunotherapy—targets β-amyloid and removes it |
| BAN2401 | Monoclonal antibody—removes amyloid protofibrils and reduces amyloid plaques |
| BIIB092 | Monoclonal antibody—removes tau and reduces tau propagation |
| LY3002813 (donanemab) | Monoclonal antibody—removes amyloid by recognizing aggregated pyroglutamate form of Aβ |
| LY3303560 (zagotenemab) | Monoclonal antibody—neutralizes soluble tau aggregates |
| Semorinemab (RO7105705) | Monoclonal antibody—removes extracellular tau |
| APH-1105 | Alpha-secretase modulator—reduces amyloid |
| Daratumumab | Monoclonal antibody—immunomodulatory that targets CD38 and regulates microglial activity |
| Dasatinib + Quercetin | Tyrosine kinase inhibitor (dasatinib) + flavonoid (quercetin)—reduces senescent cells and tau aggregation |
| IONIS MAPTRx (BIIB080) | Epigenetic, Tau Antisense oligonucleotide—reduces tau production |
| Lithium | Neurotransmitter receptors ion channel modulator—improves neuropsychiatric symptoms |
| Nilotinib | Tyrosine kinase inhibitor—promotes clearance of amyloid and tau proteins |
| Posiphen | Selective inhibitor of APP—reduces amyloid, tau, and α-synuclein production |
| PTI-125 | Filamin A protein inhibitor—reduces tau hyperphosphorylation, synaptic dysfunction, and stabilizes soluble amyloid and the α7 nicotinic acetylcholine receptor interaction |
| PQ912 | Glutaminyl cyclase (QC) enzyme inhibitor—reduces amyloid plaques and pyroglutamates Aβ production |
| Riluzole | Glutamate receptor antagonist—reduces glutamate-mediated excitotoxicity |
| Thiethylperazine (TEP) | Activates ABCC1 (ATP binding cassette subfamily C member 1 transport protein)—removes amyloid |
| Phase 1 Clinical Trials | |
| BIIB076 | Monoclonal antibody—removes tau and reduces tau propagation |
| Lu AF87908 | Monoclonal antibody—removes tau |
| anle138b | Aggregation inhibitor—reduces tau aggregation |
| RO7126209 | Monoclonal antibody—removes amyloid |
| TPI-287 | Stabilizes tubulin-binding, microtubule, and reduces cellular damage mediated by tau |