Cathy Miller

Beta-secretase inhibitors in phase I and phase II clinical trials for Alzheimer's disease

Blog Post created by Cathy Miller on Apr 25, 2019

Beta-secretase inhibitors in phase I and phase II clinical trials for Alzheimer's disease

BACE 1 is a protease that cleaves the transmembrane amyloid precursor protein and generates amyloid-β peptides that accumulate in AD brains. No known mutations are identified in the gene encoding BACE1 in AD. However, enzyme levels are elevated in AD and a single residue mutation in amyloid precursor protein protects against protein cleavage by BACE1, suggesting BACE involvement in disease pathogenesis. Drugs that can inhibit BACE1 would theoretically prevent Aβ accumulation and halt AD onset and progression. Areas covered: This review discusses clinical developments of BACE1 inhibitors and focuses on what is learned about these inhibitors as a potential treatment. Expert opinion: BACE1 inhibition as a therapeutic strategy to improve cognition in AD has been challening. Brain-penetrant BACE1 inhibitors have been developed and clinical trials are underway, both safety and efficacy are questionable. Several clinical trials suggest that BACE1 inhibition and other immunotherapies to reduce brain Aβ are insufficient to improve cognition in AD. This may be due to the emphasis on the amyloid hypothesis despite big failures. We may have to seriously consider shifting attention to therapeutic strategies other than BACE1 inhibition or reduction of Aβ alone and pay more attention to simultaneous clearance of tau and Aβ. See more at Beta-secretase inhibitors in phase I and phase II clinical trials for Alzheimer's disease. - PubMed - NCBI

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