Experimental treatments being developed to address the underlying cause of Alzheimer’s disease mostly target beta-amyloid plaques and tau protein tangles, which are thought to be the main players in cellular death in the disease.
However, a number of other compounds with different modes of action also are being developed to treat the disease. These are listed below. More information about each of them can be obtained by clicking on the link to the compound.
ABBV-8E12 (formerly C2N-8E12)
AC-1204 is a novel investigational therapy being developed by Accera that directs the body’s metabolism to provide ketones to compensate for glucose deficiency in Alzheimer’s disease.
AVP-786, developed by Avanir Pharmaceuticals, is a second-generation version of AVP-923/Nuedexta. It is currently being investigated in a Phase 3 clinical trial (NCT02442765) for the treatment of agitation in Alzheimer’s disease patients. The trial is currently recruiting participants across the U.S.
Allopregnanolone, currently being studied at the University of Southern California in a Phase 1 clinical trial (NCT02221622), is a naturally occurring brain steroid that promotes nerve stem cell proliferation and restores cognitive function.
Brexpiprazole, co-developed by Otsuka and Lundbeck, is thought to work as a partial agonist (with both blocking and stimulating activity) of serotonin 5-HT1A and dopamine D2 receptors, and as an antagonist of serotonin 5-HT2A receptors. It has already been approved to treat patients with schizophrenia and major depressive disorder (MDD).
Carvedilol, approved to treat high blood pressure and heart problems, is a nonselective “beta blocker” that works by blocking the cell-surface receptors required for nerve cell communication, preventing chemical messengers from reaching them.
Curcumin is a polyphenol derived from the herb turmeric that has been found to inhibit several disease pathways in Alzheimer’s disease.
Deep brain stimulation of the fornix
Deep brain stimulation of the fornix is a technique that uses a surgically implanted medical device that delivers mild electrical pulses to a precisely targeted area of the brain, the fornix, a major fiber bundle in the brain’s memory circuit. The approach is currently being investigated in a clinical trial (NCT03290274) in Spain.
Gemfibrozil is a fibrate therapy approved to control cholesterol levels. It has been shown to increase the levels of a type of ribonucleic acid (RNA) called microRNA-107 that is reported to be reduced in Alzheimer’s disease. It is currently being investigated in an early Phase 1 clinical trial (NCT02045056) in the U.S.
Intepirdine, developed by Axovant Sciences, is a selective antagonist of the 5-HT6 receptor. It was hoped that it could enhance cognition, memory, and learning, but failed to show improvement compared to placebo.
Liraglutide, prescribed for the treatment of diabetes, is an analog of glucagon-like peptide 1 (GLP-1) that stimulates insulin production. Thus, liraglutide is designed to increase glucose transport in the brain by increasing insulin that may potentially reduce nerve cell death. It is being investigated in a Phase 2 clinical trial (NCT01843075) in Alzheimer’s disease patients. The trial is currently recruiting participants at Imperial College London.
Lumateperone (ITI-007), developed by Intra-Cellular Therapies, selectively binds and blocks 5-HT2A receptors. It is currently being investigated for the treatment of schizophrenia, bipolar depression, and agitation in Alzheimer’s disease in a Phase 3 clinical trial (NCT02817906), which is currently recruiting participants across the U.S.
Nasal insulin consists of insulin that is atomized into a spray and can be inhaled through the nose. Insulin levels and insulin receptor signaling are believed to be reduced in Alzheimer’s disease. The treatment is currently being investigated in a Phase 1 clinical trial (NCT02462161) that is recruiting participants in North Carolina, in the U.S.
ORM-12741 is a novel orally available antagonist of alpha-2C adrenergic receptors developed by Orion Corporation for the treatment of Alzheimer’s disease. It is currently being investigated in a Phase 2 clinical trial (NCT02471196).
PXT864 is a novel repurposed synergistic combination of baclofen and acamprosate. It is designed to target the metabolic imbalance in the brain of patients with Alzheimer’s disease. It is being developed by Pharnext.
Pimavanserin, approved to treat psychosis in Parkinson’s disease, is a selective serotonin (5-HT) 2A receptor inverse agonist. It is currently being investigated by Acadia Pharmaceuticals for the treatment of psychosis in Alzheimer’s disease.
Piromelatine is a novel compound that acts as an agonist of melatonin receptors (MT1/MT2/MT3) and serotonin receptors (5-HT1A and 5-HT1D). It is being developed by Neurim Pharmaceuticals to improve sleep and cognition in Alzheimer’s.
Prazosin, an approved therapy for the treatment of high blood pressure, is an “alpha blocker” that competes with a chemical messenger called norepinephrine and blocks its binding to its receptor (alpha-1 adrenergic receptor), resulting in reduced receptor activation.
Repetitive transcranial magnetic stimulation (rTMS)
rTMS is a noninvasive tool that is reported to regulate and balance the activity of nerve cells. It is currently being studied for the treatment of AD.
Resveratrol is a polyphenol found in foods, such as red grapes, that has been reported to have neuroprotective effects.
Riluzole is an approved treatment for amyotrophic lateral sclerosis (ALS). It has been shown to modulate glutamate-mediated nerve cell communication and is thought to have neuroprotective effects. It is now being studied for the treatment of Alzheimer’s disease.
Saracatinib is an inhibitor of the Src/abl family of kinases. It is currently being studied at Yale University and across the U.S. and Canada for the treatment of AD in a Phase 2 clinical trial (NCT02167256).
S-equol is a selective agonist of estrogen receptor originally developed by Ausio Pharmaceuticals for the treatment of menopausal symptoms. It is now being studied to improve cognition in Alzheimer’s disease.
SUVN-502, developed by Suven Life Sciences, is a selective antagonist of the 5-HT6 serotonin receptor that mediates transmission of nerve signals for functions such as cognition and memory. Blocking the 5-HT6 receptor increases acetylcholine and glutamine signaling in the brain. The treatment is currently being developed as a treatment for Alzheimer’s disease.
SUVN-G3031 is an oral antagonist of histamine H3 receptor. It is being developed by Suven Life Sciences and studied as a potential treatment for Alzheimer’s and schizophrenia.
T3D-959 is an oral agonist of the receptors found in the cell nucleus called PPARδ/γ, which regulates the expression of several genes. It is being developed by T3D Therapeutics for the treatment of Alzheimer’s disease.
Telmisartan is an antagonist of the angiotensin 2 receptor that binds and blocks its function. It is marketed as a treatment for high blood pressure and currently being investigated as a potential treatment for Alzheimer’s disease.
Xanamem, developed by Actinogen Medical, blocks the activity of an enzyme called 11β-HSD1 that converts cortisone to its active form of cortisol. This enzyme is found in higher-than-normal levels in people with Alzheimer’s disease. The treatment is currently being investigated in a Phase 2 clinical trial (NCT02727699) in the U.S., Australia, and the U.K., in people with dementia due to Alzheimer’s disease.
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