Patients with Alzheimer’s disease who were given experimental medication gantenerumab experienced reductions in brain amyloid levels, researchers from Roche, Switzerland, reported in the journal Archives of Neurology. The authors stressed theirs was a small study which will need further confirmation with larger studies.

Gantenerumab is a fully human anti-Aβ monoclonal antibody in clinical development for the treatment of Alzheimer disease. Gantenerumab’s chemical formula is C6496H10072N1740O2024S42.

As background information, the authors wrote:

“Genetic and neuropathological evidence suggests that the accumulation of amyloid-β (Aβ) peptides in the brain is a key event in the pathophysiology of Alzheimer disease (AD).”

They added that several studies are currently underway which are looking at how to reduce Aβ amyloid levels in the brain.

The researchers wrote:

“We previously reported the development of gantenerumab, a potent and fully human anti-Aβ antibody that binds specifically to Aβ plaques.”

Susanne Ostrowitzki, M.D. and team set out to determine whether gantenerumab might have an impact on Aβ amyloid brain levels; they also intended to understand the mechanism of amyloid reduction. Their (small) study involved individuals with mild-to-moderate Alzheimer’s disease – it was carried out at three university medical centers.

Patients were randomly selected to receive 2 to 7 intravenous gantenerumab (60 or 200 mg) infusions every four weeks, or an infusion containing placebo. They also used brain tissue from two AD (Alzheimer’s disease) patients which was coincubated with gantenerumab as an ex vivo study. The tissues were obtained during surgical interventions to remove tumors.

The researchers wrote:

“Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. The mean [average] percent change from baseline difference relative to placebo (n = 4) in cortical brain amyloid level was -15.6 percent for the 60-mg group (n = 6) and -35.7 percent for the 200-mg group (n = 6).” The authors note that “Gantenerumab induced phagocytosis (a process the body uses to destroy dead or foreign cells) of human amyloid in a dose-dependent manner ex vivo.

Our study demonstrates that two to seven months of treatment with gantenerumab led to dose-dependent amyloid reduction in the brains of patients with AD. Additionally, our findings in the placebo-treated patients support previous reports indicating that amyloid load continues to increase in many patients with mild-to-moderate AD.”

They believe the treatment works through an “effector cell-mediated mechanism of action”.

They concluded:

“. . . it is still unclear whether any reduction in brain amyloid level will translate into clinical efficacy. A phase two clinical trial is under way to investigate whether a clinical benefit can be achieved in gantenerumab-treated patients with prodromal (early symptoms) AD.”

Written by Christian Nordqvist