Gantenerumab Lowers Brain Amyloid Levels in Alzheimer's

Phagocytosis of brain amyloid cells by gantenerumab is the most likely mechanism

TUESDAY, Oct. 11 (HealthDay News) -- Gantenerumab therapy induces dose-dependent reduction of brain amyloid levels in patients with Alzheimer's disease (AD), possibly by phagocytosis, according to a study published online Oct. 10 in the Archives of Neurology.

Susanne Ostrowitzki, M.D., from F. Hoffmann-La Roche Ltd. in Basel, Switzerland, and colleagues investigated the effect of gantenerumab therapy on Aβ amyloid levels in the brains of patients with mild-to-moderate AD, and tried to elucidate the mechanism of action. Sixteen patients were randomized to receive two to seven infusions of intravenous gantenerumab, either at 60 or 200 mg (n = 6 for each dose), or placebo (n = 4). At the end of treatment, all participants underwent ascending-dose positron emission tomographic (PET) scans and magnetic resonance imaging (MRI). Concurrently, ex vivo brain slices from patients with AD were examined by coincubating them with ascending concentrations of gantenerumab and with human microglial cells. The percent change in the in vivo ratio of regional carbon 11-labeled Pittsburgh Compound B retention, and ex vivo gantenerumab-induced phagocytosis of amyloid cells were assessed.

The investigators found that relative to placebo, the cortical amyloid levels on PET scans showed a mean percent change from baseline of −15.6 percent and −35.7 percent for the 60-mg and the 200-mg groups, respectively. MRI scans at sites with highest levels of amyloid reduction showed transient and focal areas of inflammation or vasogenic edema in two patients. Dose-dependent phagocytosis of amyloid cells was induced by gantenerumab ex vivo.

"Gantenerumab treatment resulted in a dose-dependent reduction in brain amyloid level, possibly through an effector cell-mediated mechanism of action," the authors write.

Several authors disclosed financial relationships with pharmaceutical and health care companies, including F. Hoffmann-La Roche Ltd., which supported the study.

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