One of the hallmarks of Alzheimer’s disease is the formation of protein plaques and tangles between nerve cells. These are made of so-called beta-amyloid fragments that stick together and accumulate between nerve cells, disrupting their function.
These beta-amyloid plaques are the focus of many experimental treatments that researchers are currently developing. Below is a list of the experimental treatments targeting beta-amyloid plaques. More information about each potential treatment is available by clicking on the name of the compound.
ABvac40 is an active vaccine being developed by Araclon Biotech. It consists of a fragment of beta-amyloid protein called beta-amyloid 40. It is designed to elicit an immune response against beta-amyloid plaques.
Aducanumab (BIIB037) is a monoclonal antibody that was being developed by Biogen against aggregated forms of beta-amyloid. However, the development of this treatment has been halted based on the prediction that two Phase 3 clinical trials ENGAGE (NCT02477800) and EMERGE (NCT02484547) are unlikely to meet their primary endpoints. Based on a later analysis of additional follow-up data and other supportive findings, Biogen submitted a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) requesting the therapy’s approval for the treatment of Alzheimer’s disease.
ALZT-OP1, being developed by AZ Therapies, is designed to block beta-amyloid aggregation. It is a combination regimen of two treatments already approved by the FDA: cromolyn (designated as ALZT-OP1a) and ibuprofen (designated as ALZT OP1b). It is currently being investigated in a Phase 3 clinical trial (NCT02547818) across the U.S., Australia, and Europe.
BAN2401 is a monoclonal antibody being co-developed by Eisai and Biogen Idec. It specifically binds to large beta-amyloid protofibrils (structures that precede the formation of plaques) and likely leads to their clearance. It is currently being investigated in a Phase 2 clinical trial (NCT01767311).
CAD 106 is an investigational, vaccine-based therapy being developed by Novartis. It consists of multiple copies of beta-amyloid 1-6 peptide coupled to a virus-like particle. It elicits a strong immune response while avoiding inflammatory T-cell activation. It is currently being investigated in a Phase2/3 clinical trial (NCT02565511) across the U.S., Canada, and Europe.
CNP520, developed by Novartis, is an inhibitor of an enzyme called BACE-1 (or β-secretase) that cleaves APP protein into a fragment that gives rise to beta-amyloid peptide. CNP520-mediated BACE-1 inhibition prevents Aβ formation and limits beta-amyloid deposits. The treatment is currently being investigated in a Phase 2/3 clinical trial (NCT03131453) across the world.
CT1812, developed by Cognition Therapeutics, is a small molecule that penetrates the brain and displaces toxic Aβ oligomers from neuronal receptors, allowing nerve cell communication to be restored.
Lasabecestat – LY3314814
Formerly known as AZD3293, Lasabecestat or LY3314814 is an inhibitor of the BACE1 enzyme that cleaves APP. The cleaved protein fragments stick together and form beta-amyloid plaques in Alzheimer’s. It is being developed by Eli Lilly and Company.
Lu AF20513 is an active vaccine being developed by Lundbeck. It consists of a fragment of Aβ peptide and sequences of tetanus toxin. It is designed to rouse the weak immune system of elderly populations. It is currently being investigated in a Phase 1 clinical trial (NCT02388152) in Europe.
LY3002813 is a monoclonal antibody being developed by Eli Lilly and Company. It targets Aβ aggregated in amyloid plaques. It is currently being investigated in a Phase 1 clinical trial (NCT02624778) in the U.S. and Japan.
LY3202626, developed by Eli Lilly and Company, is an inhibitor of BACE-1 that interferes with the production of beta-amyloid plaques. It is currently being investigated in a Phase 2 clinical trial (NCT02791191) across the world.
Neflamapimod is an investigational treatment being developed by EIP Pharma LLC. It specifically inhibits a protein called p38α MAPK (mitogen-activated serine/threonine protein kinase), which plays a major role in Alzheimer’s disease-associated inflammation and impairment of synapses — the points of communication between two neurons — caused by beta-amyloid plaques.
Leukine is a synthetic form of granulocyte-macrophage colony-stimulating factor that stimulates the immune system. It is already approved for several types of leukemia. It is currently being studied at the University of Colorado for the treatment of Alzheimer’s disease to reduce the accumulation of beta-amyloid.
Solanezumab – LY2062430
Solanezumab is an antibody against amyloid-beta being deeloped by Eli Lilly and Company.
Thalidomide is a molecule able to cross the blood-brain barrier and inhibit the release of tumor necrosis factor-alpha (TNF-α), which activates BACE-1.
UB 311 is a peptide vaccine being developed by United Neuroscience. It is designed to stimulate an immune response against aggregated Aβ peptides.
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