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More Disappointment on the Alzheimer’s Front

Another late-stage trial comes up empty-handed

Accera, Inc., has announced that patients with mild-to-moderate Alzheimer’s disease (AD) treated with the company’s small-molecule compound AC-1204 did not demonstrate a statistically significant difference at 26 weeks compared with patients given placebo, as measured by the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog). The formulation of AC-1204 was changed between phase 2 and phase 3 studies, and this change had the unintended consequence of lowering drug levels in patients, according to a company spokesperson.

The NOURISH AD trial was a double-blind, randomized, placebo-controlled, parallel-group study investigating the effects of daily administration of AC-1204 in subjects with mild-to-moderate AD, with an optional 26-week open-label extension. The primary and key secondary endpoints examined the effects of AC-1204 on memory and cognition, as measured by ADAS-Cog, and global function, as measured by the Alzheimer’s Disease Cooperative Study––Clinical Global Impression of Change (ADCS-CGIC), after 26 weeks of treatment among noncarriers of the epsilon 4 variant of the apolipoprotein E gene (APOE4).

Accera intends to present an analysis of the new study at the Alzheimer’s Association International Conference in London in July 2017.

In related news, scientists in South Korea have developed a metal-based substance that works like a pair of genetic scissors to cut out amyloid-beta. The aggregation of amyloid-beta peptide has been implicated as a contributor to the formation of neuritic plaques––the pathological hallmarks of AD. The new findings were published in the January 2017 issue of the Journal of the American Chemical Society.

Although various metal complexes have been suggested as potential therapeutics for patients with AD, none of them has worked effectively in vivo.

The research team found that they could hydrolyze amyloid-beta proteins using a crystal structure called tetra-N methylated cyclam (TMC). In hydrolysis, water molecules split other molecules apart. The metal-mediated TMC structure uses hydrolysis to stop the binding of amyloid-beta proteins.

In the study, four metals––cobalt, nickel, copper, and zinc––were placed at the center of the TMC structure. The scientists found that hydrolysis activity was greatest when double-layered cobalt was added to the center.

The researchers reported that the cobalt-based metal complex had the potential to penetrate the blood–brain barrier, and that hydrolysis activity against nonamyloid proteins was low.

Sources: Accera; February 28, 2017; and Medical Xpress; February 28, 2017.

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