Researchers from AgeneBio and Johns Hopkins University are working on using an investigational once-a-day medication to treat amnestic mild cognitive impairment due to Alzheimer’s disease. This drug has shown promising results in slowing brain atrophy progression in individuals with mild cognitive impairment who are not carriers of the APoE-4 genetic variant. The drug, known as AGB101, is an extended release form of the epilepsy medication levetiracetam and is designed to quiet hyperactivity in the hippocampus, a brain region critical for memory formation and retrieval.
The study conducted as part of the HOPE4MCI clinical trial evaluated the effectiveness of AGB101 in treating mild cognitive impairment in 164 individuals with Alzheimer’s disease. Results showed that participants who were non-carriers of the APoE-4 allele and treated with AGB101 demonstrated a 40% reduction in disease progression on the Clinical Dementia Rating scale over an 18-month period compared to those who received a placebo. Slowing disease progression in the early stages of mild cognitive impairment can help individuals maintain independent living for longer and delay the onset of dementia, ultimately reducing the need for nursing home care.
In addition to its clinical-cognitive benefits, AGB101 also significantly reduced atrophy of the entorhinal cortex in the brains of individuals not carrying the APoE-4 allele. The entorhinal cortex is a key brain region involved in memory and time perception, and its atrophy is a hallmark of Alzheimer’s disease progression. By slowing atrophy in this region, the drug shows promise in slowing neurodegeneration and disease progression in individuals with mild cognitive impairment due to Alzheimer’s disease.
During the study, researchers found that AGB101 treatment matched the efficacy of FDA-approved biologics for prodromal Alzheimer’s disease and exceeded current data on Alzheimer’s therapeutics by reducing atrophy of the entorhinal cortex. This suggests that the drug may offer a significant benefit for individuals with mild cognitive impairment, especially those who do not carry the APoE-4 allele. While more studies are needed to confirm these findings, the potential of AGB101 in slowing disease progression and its limited side effects in this population hold significant promise for the treatment of Alzheimer’s disease.
Scott Kaiser, MD, a geriatrician and Director of Geriatric Cognitive Health, sees this study as encouraging and promising in the face of a projected tripling of worldwide dementia cases by 2050. He believes that adopting a chronic disease management approach to Alzheimer’s, similar to diabetes or hypertension, with a range of treatments targeting different disease mechanisms, could usher in a new era of effective treatment. Kaiser also notes the value of repurposing existing drugs and investing in preclinical research to identify new treatment targets and better understand the underlying pathways of Alzheimer’s disease.
Overall, the research on AGB101 and its potential in treating mild cognitive impairment due to Alzheimer’s disease offers hope for individuals at risk of developing dementia. By focusing on slowing disease progression and preserving cognitive function in the early stages of the disease, this investigational medication could make a significant impact in delaying the onset of dementia and improving quality of life for those affected by Alzheimer’s. Further studies to confirm these findings and explore the long-term effects of AGB101 are needed to fully understand its potential as a treatment for Alzheimer’s disease.
