阿杜那单抗 (Aduhelm)

概览

Aducanumab is a monoclonal antibody indicated in the treatment of Alzheimer's disease.

作用机制

Alzheimer's disease is a neurodegenerative disease. Part of the pathology of Alzheimer's disease is the presence of plaques forming extracellularly in the brain. These plaques are mostly composed of amyloid-β, a peptide of varying length formed by the cleavage of the amyloid precursor protein. The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-β oligopeptides in the brain drives the pathogenesis of Alzheimer's disease. Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β at amino acids 3-7. The amyloid-β residues Phe4, His6, Glu3, and Arg5 are responsible for the majority of the contact between amyloid-β and aducanumab's Fab region. Data from studies in mice and humans shows aducanumab treatment reduces amyloid-β, however human trials show non-significant changes in amyloid-β40 and amyloid-β42 across a dose range of 0.3-30 mg/kg and an increase in amyloid-β40 and amyloid-β42 at 60 mg/kg. Aducanumab treatment is associated with slowing the rate of progression of Alzheimer's disease, based on Mini-Mental State Examination, Clinical Dementia Rating, and levels of p-tau in the cerebrospinal fluid.

适应症

Aducanumab is indicated for the treatment of Alzheimer’s disease. Treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.

• Alzheimer's Disease (AD)