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New Approach Delays Onset of Alzheimer’s Dementia

First clinical trial to reduce hippocampal over-activity at pre-dementia stage

AGB101, a once-daily low-dose formulation of levetiracetam, restored brain-network function and significantly improved memory in elderly patients with amnestic mild cognitive impairment (aMCI), the pre-dementia stage of Alzheimer’s disease, according to investigators at Johns Hopkins University. Levetiracetam is an anti-epileptic drug commercialized for more than a decade.

Findings from the stage II study were reported in the journal NeuroImage: Clinical.

AGB101 will be given to patients at approximately one-fifteenth of the dose most commonly prescribed for epilepsy, according to the drug’s developer, AgeneBio. The company expects to initiate a phase III clinical program for AGB101in the second half of 2015. If approved by the FDA, AGB101 would be the first therapeutic that reduces hippocampus over-activity and could be the first treatment to slow progression to, and delay the onset of, Alzheimer’s dementia.

Hippocampal over-activity is a key characteristic of the aMCI stage of Alzheimer’s disease and is the best predictor of subsequent cognitive decline and progression to Alzheimer’s dementia.

The new phase II study was the first to target hippocampal over-activity during aMCI. The randomized double-blind trial with subject crossover employed blood oxygen level- dependent (BOLD) contrast imaging, a method used in functional magnetic resonance imaging (fMRI), to detect the effects of drug treatment across a range of doses on brain function together with memory performance. The study enrolled 69 patients; 54 aMCI patients and 17 control patients completed the trial. The results showed that AGB101 (125 or 250 mg daily) reduced excess hippocampal activity to the normal range and significantly improved memory performance in aMCI patients.

In the U.S., 5.6 million people have aMCI, the symptomatic, pre-dementia stage of Alzheimer’s disease characterized by significant loss of memory, and this population is expected to double by 2030. Alzheimer’s disease currently costs Medicare and Medicaid $150 billion in direct medical costs annually.

Sources: AgeneBio; March 11, 2015; and NeuroImage: Clinical; 2015.

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