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NIH Backing Alzheimer’s Onset Drug Trial

Michela Gallagher

Michela Gallagher (Johns Hopkins University)

15 September 2015. National Institute on Aging, part of National Institutes of Health, is funding a late-stage clinical trial testing a current epilepsy drug as a treatment to delay the early onset of Alzheimer’s symptoms. The $7.5 million grant, part of NIH’s national plan to address Alzheimer’s disease, supports the trial testing a low-dose formulation of levetiracetam conducted by the biopharmaceutical company AgeneBio and Johns Hopkins University.

The trial will test levetiracetam’s ability to prevent or delay symptoms of amnestic mild cognitive impairment, marked by memory, language, and judgement difficulties, considered greater than expected age-related problems, but not reaching the severity of dementia. AgeneBio says amnestic mild cognitive impairment affects about 5.6 million people in the U.S. and 25 million worldwide.

Amnestic mild cognitive impairment is considered an indicator and predictor of Alzheimer’s disease. Because levetiracetam has been on the market for more than a decade — marketed by UCB Pharmaceuticals as Keppra and in generic form — it is well-tolerated and has a known safety profile.

AgeneBio’s drug candidate code-named AGB101 sharply reduces the normal dose of levetiracetam to about 1/12th of that prescribed for epilepsy.  AGB101 is designed to reduce hyperactivity in the hippocampus, the part of the brain associated with memory. Overactivity in the hippocampus is believed to disrupt normal memory functions, beginning in the entorhinal cortex, considered the gateway for making memories.

The trial is led by AgeneBio’s founder Michela Gallagher, a professor of psychology and neuroscience at Johns Hopkins University in Baltimore, whose research includes the neurobiological basis of cognitive impairment in the aging process. Gallagher shares the project’s leadership with Marilyn Albert, director of the Johns Hopkins Alzheimer’s Disease Research Center.

In March, AgeneBio reported on an intermediate-stage trial of AGB101 with 69 individuals having amnestic mild cognitive impairment, or aMCI. Of that group, 54 randomly were assigned to receive AGB101 once a day at 1 of 3 dosage levels and 17 receiving a placebo. Participants’ cognitive functions were assessed on several tests and indexes, including mental status, selective memory, paired associations, visual retention, and basic activities of daily living. The trial also tested participants’ hippocampus activity, using functional MRI that provides images of neural activity in the brain.

The findings show patients receiving AGB101 at all dosage levels scoring higher on the memory tests than participants receiving the placebo. Likewise, patients receiving AGB101 show reduced hippocampus activity to normal ranges compared to the placebo group. The researchers found no differences between the two highest dosages — 125 and 250 milligrams — of AGB101 on either the memory tests or hippocampus activity results.

Gallagher notes in a company statement, “The state of the science points to hippocampal overactivity in aMCI as a strong predictor of progression to Alzheimer’s dementia and the earliest point at which this pre-dementia condition can be diagnosed before significant irreversible neurodegeneration kills brain cells. We expect our upcoming trial to demonstrate efficacy in preserving cognition and memory in aMCI patients while delaying progression to the clinical stage of Alzheimer’s dementia.”

The new trial is also funded by a $900,000 grant from Alzheimer’s Drug Discovery Foundation, as reported in January 2015 in Science & Enterprise. The study is expected to begin in 2016.

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