Table 2 Anti-AD drugs with anti-ageing properties in trials
From: The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing
Candidate drugs | Relevant AD hallmark of target | Mechanism of action | Outcome | Current clinical trial |
|---|---|---|---|---|
Lecanemab | Loss of proteostasis | Monoclonal antibody directed at Aβ plaques and oligomers | Reduces Aβ deposition | Phase 3 (NCT03887455) |
Aducanumab | Loss of proteostasis | Monoclonal antibody directed at Aβ plaques and oligomers | Reduces Aβ deposition and controls inflammation | Phase 3 (NCT04241068) |
Donanemab | Loss of proteostasis | Monoclonal antibody specific for the pyroglutamate form of Aβ | Reduces Aβ deposition | Phase 3 (NCT04437511) |
Donanemab & Aducanumab | Loss of proteostasis | Combination of two monoclonal antibodies | Reduces Aβ deposition | Phase 3 (NCT05108922) |
Simufilam (PTI-125) | Loss of proteostasis | Filamin A protein inhibitor | Stabilizes the interaction between amyloid-alpha-7 and nicotinic receptor | Phase 3 (NCT04994483) |
Gantenerumab | Loss of proteostasis | Monoclonal antibody directed at Aβ plaques and oligomers | Reduces Aβ deposition | Phase 3 (NCT03444870) |
TRx0237 | Loss of proteostasis | Inhibitor of tau protein aggregation | Reduces tau protein aggregation | Phase 3 (NCT04770220) |
Valiltramiprosate (ALZ-801) | Loss of proteostasis | Prodrug of tramiprosate | Inhibits the aggregation of Aβ into toxic oligomers | Phase 3 (NCT04770220) |
ACI-35 | Loss of proteostasis | Active immunotherapy targeting tau | Reduces tau protein aggregation | Phase 2 (NCT04445831) |
Nilotinib BE | Disabled macroautophagy | Tyrosine kinase inhibitor; autophagy enhancer | Increases clearance of Aβ and tau | Phase 3 (NCT05143528) |
Losartan and Amlodipine and Atorvastatin + exercise | Deregulated nutrient sensing | Angiotensin II receptor blocker (losartan), calcium channel blocker (amlodipine) and cholesterol agent (atorvastatin) | Regulates vascular energy metabolism | Phase 3 (NCT02913664) |
Metformin | Deregulated nutrient sensing | Insulin sensitizer | Improves glucose metabolism in the CNS | Phase 3 (NCT04098666) |
Semaglutide | Deregulated nutrient sensing | GLP-1 agonist | Reduces neuroinflammation and improves insulin signalling in the brain | Phase 3 (NCT04777396) |
Tricaprilin | Mitochondrial dysfunction | Caprylic triglyceride | Induces ketosis and improves mitochondrial and neuronal function | Phase 3 (NCT03446001) |
MitoQ | Mitochondrial dysfunction | Mitochondria‐targeting antioxidant | Reduces systemic oxidative stress and increases cerebral oxygenation | Phase 1 (NCT03514875) |
AGB101 (low-dose levetiracetam) | Cellular senescence | Synaptic plasticity/neuroprotection | Reduces Aβ-induced neuronal overactivity | Phase 3 (NCT03486938) |
Atuzaginstat (COR388) | Cellular senescence | Synaptic plasticity/neuroprotection | Reduces Aβ-induced neuronal overactivity | Phase 3 (NCT03823404) |
Dasatinib + Quercetin | Cellular senescence | Tyrosine kinase inhibitor (dasatinib) and flavonoid (quercetin) | Decreases the number of senescent cells and tau aggregation | Phase 1 (NCT04063124 and NCT04785300) Phase 2 (NCT04685590) |
Deferiprone | Cellular senescence | Iron-chelating agent | Reduces the amount of reactive oxygen species | Phase 2 (NCT03234686) |
AVP-786 | Altered intercellular communication | Sigma 1 receptor agonist and NMDA receptor antagonist | Controls neuropsychiatric symptoms | Phase 3 (NCT03393520) |
AXS-05 | Altered intercellular communication | NMDA receptor antagonist | Controls neuropsychiatric symptoms | Phase 3 (NCT04797715) |
Donepezil | Altered intercellular communication | Acetylcholinesterase inhibitor | Improves cognitive impairment | Phase 3 (NCT04661280) |
Caffeine | Altered intercellular communication | Adenosine antagonist; non-specific phosphodiesterase inhibitor | Improves cognitive impairment | Phase 3 (NCT04570085) |
Blarcamesine (ANAVEX2-73) | Chronic inflammation | M2 autoreceptor antagonist | Improves oxidative stress, protein misfolding, mitochondrial dysfunction and inflammation | Phase 3 (NCT03790709) |
Hydralazine | Chronic inflammation | Free radical scavenger | Controls inflammatory response caused by oxidative stress | Phase 3 (NCT04842552) |
Icosapent ethyl (IPE) | Chronic inflammation | Purified form of the omega-3 fatty acid EPA | Improves synaptic function and reduces inflammation | Phase 3 (NCT02719327) |
NE3107 | Chronic inflammation | MAPK-1/3 inhibitor | Reduces activation of proinflammatory NFκB | Phase 3 (NCT04669028) |
Canakinumab | Chronic inflammation | Anti-IL-1β monoclonal antibody | Reduces neuroinflammation | Phase 2 (NCT05189106) |
Baricitinib | Chronic inflammation | Janus kinase inhibitor | Reduces neuroinflammation | Phase 2 (NCT05189106) |
GV-971 | Dysbiosis | Algae-derived acidic oligosaccharides | Regulates bacterial imbalance and reduces peripheral and central inflammation | Phase 3 (NCT04520412) |