Aducanumab

History

Aducanumab(brand name Aduhelm) was discovered by Biogen and Eisai, is an anti-amyloid drug designed to treat Alzheimer's disease. It is a monoclonal antibody that targets aggregated forms (plaque)[3][4] of amyloid beta (Aβ) found in the brains of people with Alzheimer's disease to reduce its buildup. Granted accelerated approval by the United States Food and Drug Administration (FDA) in June 2021, aducanumab is the first AD treatment to receive formal regulatory clearance since 2003.

Uses

Aducanumab (BIIB037) is a human monoclonal antibody that selectively targets aggregated amyloid-beta (Aβ). Aducanumab shows brain penetration, and can be used for Alzheimer's disease (AD) research[1].

Enzyme inhibitor

This high-affinity, fully human IgG1 monoclonal antibody (MW = 149.5 kDa; CAS 1384260-65-4), also known by the developmental code name BIIB037, selectively targets aggregated forms of b-amyloid protein (EC50 = 0.1 nM), while showing weak binding to Ab monomer. In the brains of transgenic mice, aducanumab preferentially binds to parenchymal Aβ over vascular Aβ deposits, consistent with the lack of effect on vascular Aβ following chronic dosing. Aducanumab dose-dependently reduces amyloid deposition in six cortical regions of the brain. chAducanumab, a murine IgG2a/κ chimeric analogue, dose-dependently reduces Aβ measured in brain homogenates by up to 50% relative to the vehicle control in the diethylamine fraction that extracted soluble monomeric and oligomeric forms of Aβ40 and Aβ42, and in the guanidine hydrochloride fraction that extracted insoluble Aβ fibrils. The clearance of Aβ deposits was accompanied by enhanced recruitment of microglia. Together with the reduced potency of the aglycosylated form of chaducanumab and the ex vivo phagocytosis data, such findings suggest that FcγR-mediated microglial recruitment and phagocytosis played an important role in Aβ clearance in these models. Activated microglia appeared to encapsulate the remaining central dense core of plaques in treated animals, possibly isolating them from the surrounding neurophil.

in vivo

References

[1] Sevigny J, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature. 2016 Sep 1;537(7618):50-6. DOI:10.1038/nature19323
[2] Kastanenka KV, et al. Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. J Neurosci. 2016 Dec 14;36(50):12549-12558. DOI:10.1523/JNEUROSCI.2080-16.2016