Researchers from AgeneBio and Johns Hopkins University have been studying the use of a once-a-day investigational medication to treat amnestic mild cognitive impairment due to Alzheimer’s disease, which can be the first sign of the disease for many individuals. The drug, known as AGB101, is an extended-release form of the epilepsy medication levetiracetam that has been found to slow brain atrophy progression in people with mild cognitive impairment due to Alzheimer’s disease who do not carry the APoE-4 genetic variant. The hyperactivity in the hippocampus, a brain region critical for memory creation and retrieval, contributes to memory impairment and disease progression in these patients. This drug aims to quiet this hyperactivity and bring brain activity levels down to those seen in cognitively normal older adults.
In a phase 2b clinical trial, researchers found that participants with mild cognitive impairment who were non-carriers of the ApoE-4 allele and treated with AGB101 showed a 40% reduction in progression on the Clinical Dementia Rating scale over 18 months compared to those who received a placebo. This represents a significant retention of cognitive and daily functioning for patients in the early stages of the disease, allowing them to sustain independent living and delay dementia onset. Additionally, AGB101 significantly reduced atrophy of the entorhinal cortex in the brains of non-carriers of the ApoE-4 allele, which plays a crucial role in memory and time perception. Slowing atrophy in this brain region is considered evidence of slowing disease progression, providing hope for effective Alzheimer’s disease therapies.
The study showed that AGB101 not only matched the efficacy of FDA-approved biologics in clinical-cognitive progression in prodromal Alzheimer’s disease but also surpassed currently published data for Alzheimer’s disease therapeutics by reducing atrophy of the entorhinal cortex. This suggests that the treatment slows neurodegeneration and offers a promising approach for patients with mild cognitive impairment due to Alzheimer’s disease who do not carry the ApoE-4 allele. The potential substantial effect of AGB101 in this population, along with minimal side effects, holds significant promise for future treatments for Alzheimer’s disease. The findings are encouraging and offer hope for tackling the increasing global burden of dementia, with potentially multiple treatments targeting different underlying mechanisms.
Scott Kaiser, MD, a geriatrician and Director of Geriatric Cognitive Health, emphasized the importance of investing in both new drug research and preclinical research to better understand the underlying mechanisms of Alzheimer’s disease and identify robust treatment targets. The study’s focus on repurposing an existing drug at a lower dose highlights the potential for developing effective treatments through a variety of approaches. By targeting different mechanisms underlying Alzheimer’s disease, researchers aim to create a future where the condition is managed like a chronic disease with a range of treatment options. This innovative approach offers promise for improving outcomes for individuals with mild cognitive impairment due to Alzheimer’s disease, potentially delaying disease progression and reducing the need for nursing home care.
As worldwide dementia cases are projected to triple by 2050, there is a pressing need for effective strategies to prevent and treat Alzheimer’s disease and related cognitive impairments. Through ongoing research and clinical trials, such as the HOPE4MCI study on AGB101, researchers hope to develop a comprehensive array of treatments that address different aspects of the disease. By targeting various mechanisms associated with Alzheimer’s disease, including hippocampal hyperactivity and brain atrophy, researchers aim to provide more personalized and effective therapies for individuals with mild cognitive impairment. The development of innovative treatments like AGB101 offers hope for improving outcomes and quality of life for individuals at risk of Alzheimer’s disease, highlighting the importance of continued research and investment in identifying novel therapeutic approaches.
