From: Repurposed agents in the Alzheimer’s disease drug development pipeline
Agent name | Phase | Agent mechanism class | Therapeutic purpose under study | Drug class | FDA-approved indication(s) | Therapeutic field | ClinicalTrials.gov ID(s) (EudraCT ID) |
---|---|---|---|---|---|---|---|
Benfotiamine | II | Metabolic | Improve multiple cellular processes; minimize decline in glucose utilization (DMT) | Synthetic thiamine | Diabetic nephropathy; type 2 diabetes | Antidiabetic | NCT02292238 |
Candesartan | II | Anti-amyloid, neuroprotective, metabolic | Improve vascular function and reduce amyloid (DMT) | Angiotensin II Receptor Blocker | Hypertension; heart failure | Cardiovascular | NCT02646982 |
Cilostazol | II | Neuroprotective | Reduce accumulation of amyloid and reduce tau phosphorylation; improve cerebral circulation (DMT) | Antiplatelet | Intermittent claudication | Hematologic-oncologic | NCT02491268 |
Dapagliflozin | I/II | Metabolic | Improve insulin sensitivity (DMT) | Sodium-glucose co-transporter 2 inhibitor | Adjunct therapy for type 2 diabetes | Antidiabetic | NCT03801642 |
Daratumumab | II | Anti-inflammatory | Broad range immunomodulatory effects; regulate microglia (DMT) | Human antibody targeting CD38 | Multiple myeloma | Hematologic-oncologic | NCT04070378 |
Dasatinib + Quercetin (Combo) | I/II | Anti-inflammatory | Senolytic therapy approach to reduce senescent cells and tau aggregation (DMT) | Tyrosine kinase inhibitor + antioxidant/anti-inflammatory (Flavonoid) | Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase | Hematologic-oncologic | NCT04063124 |
Deferiprone | II | Anti-Amyloid, neuroprotective | Reduce reactive oxygen species that damage neurons; effect on amyloid and BACE pathology (DMT) | Iron chelator | Iron overload (thalassemia syndromes) | Hematologic-oncologic | NCT03234686 |
Dronabinol | II | Neurotransmitter-based | Improve neuropsychiatric symptoms (agitation) | Cannabinoid | Anorexia (associated with AIDS); nausea/vomiting (associated with chemotherapy) | Cannabinoid | NCT02792257 |
Insulin glulisine | II | Metabolic | Enhance cell signaling and growth; promote neuronal metabolism (DMT) | Insulin | Diabetes | Antidiabetic | NCT02503501 |
Lenolidomide | II | Anti-inflammatory | Reduce inflammatory cytokines (TNF-a, IL-6, IL-8); reduce inflammatory and AD-associated biomarkers; improve cognition (DMT) | Anti-neoplastic | Multiple myeloma | Hematologic-oncologic | NCT04032626 |
Levetiracetam | II | Neuroprotective | Reduce amyloid induced neuronal hyperactivity (DMT) | Anticonvulsant | Adjunct therapy for partial-onset seizures; juvenile myoclonic epilepsy; primary generalized tonic-clonic seizures | Neurologic | NCT03489044 (2016–003109-32) |
Levetiracetam | II | Neuroprotective | Reduce amyloid induced neuronal hyperactivity (DMT) | Anticonvulsant | Adjunct therapy for partial-onset seizures; juvenile myoclonic epilepsy; primary generalized tonic-clonic seizures | Neurologic | NCT02002819 |
Levetiracetam | II | Neuroprotective | Reduce amyloid induced neuronal hyperactivity (DMT) | Anticonvulsant | Adjunct therapy for partial-onset seizures; juvenile myoclonic epilepsy; primary generalized tonic-clonic seizures | Neurologic | NCT03875638 |
Levetiracetam (AGB101) | II | Neuroprotective | Reduce amyloid induced neuronal hyperactivity (DMT) | Anticonvulsant | Adjunct therapy for partial-onset seizures; juvenile myoclonic epilepsy; primary generalized tonic-clonic seizures | Neurologic | NCT03461861 |
Liraglutide | II | Metabolic | Enhance cell signaling; improve CNS glucose metabolism (DMT) | Glucagon-like peptide-1 agonist | Adjunct therapy for type 2 diabetes; risk reduction of major cardiovascular events | Antidiabetic | NCT01843075 (2013-000962-13) |
Lithium | II | Neurotransmitter-based | Improve neuropsychiatric symptoms (agitation/aggression with or without psychosis) | Antimanic | Bipolar disorder | Psychiatric | NCT02129348 |
Leuprolide depot | II | Metabolic | Alleviates negative effects of elevated GnRH and gonadtropins on the brain (DMT) | Gonadotropin-releasing hormone agonist | Endometriosis; uterine leiomyomata | Hormonal | NCT03649724 |
Montelukast (buccal film) | II | Anti-inflammatory | Reduce inflammatory pathways (neuronal injury, blood-brain barrier integrity, amyloid-ß accumulation); effect on cognition and AD biomarkers (DMT) | Leukotriene receptor antagonist | Asthma; exercise-induced bronchoconstriction; allergic rhinitis | Anti-inflammatory | NCT03402503 |
Montelukast (tablet) | II | Anti-inflammatory | Reduce inflammatory pathways that mediate neuronal injury, blood-brain barrier integrity, amyloid-ß accumulation (DMT) | Leukotriene receptor antagonist | Asthma; exercise-induced bronchoconstriction; allergic rhinitis | Anti-inflammatory | NCT03991988 |
Nicotinamide | II | Anti-tau, neuroprotective | Reduce tau-induced microtubule depolymerization; reduce phosphorylation of tau (DMT) | Vitamin B3 | Pellagra | Vitamin | NCT03061474 |
Nicotine (transdermal patch) | II | Neurotransmitter-based | Enhance acetylcholine signaling (cognitive enhancer) | Alkaloid | Smoking cessation withdrawal symptoms | Alkaloid | NCT02720445 |
Nilotinib | II | Anti-amyloid, anti-tau | Autophagy enhancer; promotes clearance of amyloid and tau proteins (DMT) | Tyrosine kinase inhibitor | Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase | Hematologic-oncologic | NCT02947893 |
Perindopril | II | Neuroprotective, anti-inflammatory | Improves vascular functioning (DMT) | Angiotensin-converting-enzyme inhibitor | Essential hypertension; stable coronary artery disease | Cardiovascular | NCT02085265 |
Prazosin | II | Neurotransmitter-based | Improve neuropsychiatric symptoms (agitation) | Alpha-receptor antagonist | Hypertension | Cardiovascular | NCT03710642 |
Rifaximin | II | Anti-inflammatory | Improve cognition and function by lowering blood ammonia; lower circulatory pro-inflammatory cytokines secreted by harmful gut bacteria (DMT) | Non-systemic antibiotic | Traveler’s diarrhea; overt hepatic encephalopathy; irritable bowel syndrome (diarrhea subtype) | Infectious disease | NCT03856359 |
Riluzole | II | Neuroprotective | Reduce glutamate-mediated excitotoxicity (DMT) | Benzothiazole | Amyotrophic lateral sclerosis | Neurologic | NCT01703117 |
Sagramostim | II | Anti-amyloid, neuroprotective | Stimulates innate immune system to remove amyloid pathology; increase neuronal connectivity (DMT) | Human granulocyte-macrophage colony-stimulating factor | Bone marrow stimulation | Hematologic-oncologic | NCT01409915 |
Sodium phenylbutyrate | II | Neuroprotective | Blocks nerve cell death and modulates neuroinflammation (DMT) | Anti-hyperammonemia | Adjunct for chronic urea cycle disorders | Genetics | NCT03533257 |
Tacrolimus | II | Neuroprotective | Prevents amyloid-ß dendritic spine loss; normalizes cranial nerve activity in the brain (DMT) | Calcineurin inhibitor | Prevent rejection of organ transplants | Immunologic | NCT04263519 |
Telmisartan | II | Neuroprotective, anti-inflammatory | Improves vascular functioning (DMT) | Angiotensin II Receptor Blocker | Hypertension; diabetic neuropathy; risk reduction of stroke | Cardiovascular | NCT02085265 |
Thiethylperazine | II | Anti-amyloid | Activates transport protein ABCC1 and enhances transport amyloid-ß peptides from the brain into the blood (DMT) | Phenothiazine | Nausea/vomiting | Neurologic | NCT03417986 (2014-000870-20) |
Valacyclovir | II | Neuroprotective, anti-inflammatory | Reduce amyloid-ß aggregation by preventing overproduction of amyloid in response to infection (DMT) | Antiviral (nucleoside analog) | Herpes labialis; genital herpes | Infectious disease | NCT03282916 |
Valacyclovir | II | Neuroprotective, anti-inflammatory | Reduce amyloid-ß aggregation by preventing overproduction of amyloid in response to infection (DMT) | Antiviral (nucleoside analog) | Herpes labialis; genital herpes | Infectious disease | NCT02997982 |