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06-09-2016 | Alzheimer's disease | News | Article

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Antibody attacks beta-amyloid build up in early Alzheimer’s patients

medwireNews: Researchers have developed a human monoclonal antibody that selectively targets aggregated beta-amyloid (Aβ) and reduces its build up in the brains of patients with early-stage Alzheimer’s disease (AD).

Among 165 patients with prodromal or mild AD, Aβ visible by positron emission tomography (PET) was significantly reduced in the brains of those randomly assigned to receive monthly intravenous infusions of the antibody, aducanumab, for a year.

And although the phase Ib safety and tolerability trial was not designed to evaluate the effect of aducanumab on cognitive decline, it showed a benefit, note authors Roger Nitsch (University of Zurich, Switzerland), Alfred Sandrock (Biogen, Cambridge, Massachusetts, USA) and colleagues.

The effect of the antibody on Aβ was significant and dose-dependent, with the greatest decline seen with the highest dose of 10 mg/kg, decreasing from an average PET standard uptake value ratio (SUVR) of 1.44 at baseline to 1.16 after 54 weeks.

This value is near to the purported quantitative cutoff point of 1.10 that discriminates between positive and negative scans, the researchers point out in Nature.

The average SUVR at 54 weeks was 1.25 and 1.34 with 6 mg/kg and 3 mg/kg of aducanumab, respectively. By contrast, the change in Aβ was minimal among the 40 patients assigned to placebo.

In a related comment, Eric Reiman (Banner Alzheimer’s Institute, Phoenix, Arizona, USA) says the “trial provides convincing evidence that aducanumab can enter the brain, target Aβ fibrils and substantially reverse plaque deposition - a major advance.”

He says that “aducanumab’s unusually pronounced plaque-busting effects”, which were also seen in preclinical trials of transgenic mice, are likely to be due to its unusually high selectivity and affinity for Aβ42 fibrils and oligomers and the way it enlists microglia to engulf and clear Aβ fibrils.

In all, 125 patients completed treatment while 40 discontinued, mostly due to adverse events (22 patients) and withdrawal of consent (14 patients).

The most common adverse events were amyloid-related imaging abnormalities. These occurred in 47% of patients taking 10 mg/kg of the antibody and 37% of those taking the 6 mg/kg dose, compared with 5% of the patients given placebo, and were more common in APOE ε4 carriers.

The cognitive effects were evident in patients treated with aducanumab whose SUVR score decreased by at least one standard deviation relative to placebo-treated patients after a year of treatment.

They experienced a stabilisation in clinical decline in terms of scores on the Clinical Dementia Rating Sum of Boxes and the Mini–Mental State Examination, with the greatest effects seen with the highest dose.

“If these preliminary cognitive findings are confirmed in larger and more-definitive clinical trials, which are now under way, it would provide a shot in the arm in the fight against Alzheimer’s disease and compelling support for the amyloid hypothesis”, says Reiman.

He concludes that “confirmation that an anti-Aβ treatment slows cognitive decline would be a game-changer for how we understand, treat and prevent Alzheimer’s disease. Now is the time to find out.”

By Lucy Piper

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016

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