Researchers from AgeneBio and Johns Hopkins University are currently studying the use of a once-a-day investigational medication to treat amnestic mild cognitive impairment due to Alzheimer’s disease. This drug has shown promise in slowing brain atrophy progression in individuals with mild cognitive impairment who do not carry the APoE-4 genetic variant. The CEO of AgeneBio, Michela Gallagher, explains that patients with mild cognitive impairment often experience hyperactivity in the hippocampus, a brain region critical for memory. This hyperactivity contributes to memory impairment and disease progression.
The investigational drug, AGB101, is an extended release form of the epilepsy medication levetiracetam and works by quieting the hyperactivity in the brain, bringing it down to levels seen in cognitively normal older adults. In a phase 2b clinical trial known as HOPE4MCI, 164 individuals with Alzheimer’s disease were treated with AGB101 to evaluate its efficacy in treating mild cognitive impairment. Results showed that non-carriers of the APoE-4 allele treated with AGB101 experienced a 40% reduction in progression on the Clinical Dementia Rating scale over 18 months compared to those treated with placebo. This suggests a meaningful retention of cognitive and daily functioning in patients over time.
In addition to cognitive benefits, AGB101 also significantly reduced atrophy of the entorhinal cortex in individuals who do not carry the APoE-4 allele. The entorhinal cortex is associated with memory and time perception and is an area where Alzheimer’s pathology accumulates early in the disease. Slowing atrophy in this region is seen as evidence of slowing disease progression. The study showed that AGB101 not only matched the efficacy of FDA-approved treatments for Alzheimer’s disease but exceeded any currently published data by reducing atrophy in the entorhinal cortex, suggesting a potential to slow neurodegeneration.
Board-certified geriatrician Scott Kaiser finds this study very promising and encouraging. With the global increase in dementia cases expected in the coming years, innovative approaches like AGB101 provide hope for effective treatments for Alzheimer’s disease and cognitive impairment. Kaiser notes that potential treatments targeting different underlying mechanisms could lead to a future where Alzheimer’s disease is treated as a chronic condition with a variety of approaches. The use of existing drugs, repurposed for Alzheimer’s treatment, highlights the importance of preclinical research in identifying new pathways and treatment targets for the disease.
The promising results of the study suggest that AGB101 has the potential to delay progression of mild cognitive impairment due to Alzheimer’s disease, allowing individuals to maintain independent living and delay the onset of dementia. With further studies needed to confirm these findings, the use of AGB101 in individuals who do not carry the APoE-4 allele holds significant promise for the treatment of Alzheimer’s disease. The approach of targeting hippocampal hyperactivity with an existing drug offers hope for a new and effective treatment option for individuals with mild cognitive impairment. Overall, the study underscores the importance of continued research and innovation in the field of Alzheimer’s disease to develop effective therapies for those affected by the condition.
