A groundbreaking study led by researchers from University Hospitals, Case Western Reserve University, and the Cleveland VA has challenged the long-held belief that Alzheimer’s disease is irreversible. The research team successfully reversed advanced Alzheimer’s in mice, achieving full cognitive recovery by restoring the brain’s energy balance. The findings, published in Cell Reports Medicine, mark a significant milestone in the quest for effective treatments for this debilitating condition.
Dr. Andrew Pieper, director of the Brain Health Medicines Center at University Hospitals and senior author of the study, expressed optimism regarding the implications of their work. He stated, “The key takeaway is a message of hope — the effects of Alzheimer’s disease may not be inevitably permanent. The damaged brain can, under some conditions, repair itself and regain function.”
The research centers around NAD+, a cellular energy molecule that diminishes with age, particularly in Alzheimer’s patients. The team discovered that NAD+ levels drop significantly in the brains of those affected by the disease. By administering a compound known as P7C3-A20, developed in Pieper’s lab, they were able to stabilize NAD+ levels in two distinct mouse models of Alzheimer’s. The results were remarkable; not only did the progression of the disease halt, but cognitive function was fully restored.
What sets this approach apart from current treatments is its independence from amyloid-targeting therapies, which have been the primary focus in Alzheimer’s research. Pieper emphasized, “I want to stress that it’s independent of the amyloid approach which is being championed right now by a lot of people in the Alzheimer’s community. It could work on its own, potentially.”
The compound operates differently than typical over-the-counter NAD+ supplements. Pieper explained, “Our chemical compound stabilizes NAD homeostasis in the cell. It doesn’t ever elevate it to higher than normal physiologic levels, and that is desirable because you can be assured of safety in that way.” He noted that some over-the-counter supplements may increase NAD+ production too much, potentially posing risks.
Pieper illustrated the importance of maintaining stable NAD levels with a car analogy: “If your gas tank is full, you’re always equipped to go faster suddenly if you need to, or pull a heavier load or go up a hill. If you’re always running on empty, then all of a sudden if you come across a big hill or if you suddenly have an increased workload, there’s a chance that you’re going to run out of gas.”
The research team has founded a company named Glengary Brain Health to advance the treatment toward human trials. While the compound has shown efficacy in mice and no safety issues in studies lasting up to one year in monkeys, it will require chemical modifications before it can be tested in humans. Pieper aims to have a version ready for phase one safety trials within approximately 18 months.
The implications of this research extend beyond Alzheimer’s. Pieper believes that the approach could also be effective for various forms of neurodegeneration and dementia, including traumatic brain injury. He stated, “We view Alzheimer’s as the biggest problem. It’s an emergency, if you will, for our species.”
Despite the promising results in mice, Pieper is cautious about translating these findings to humans. “Alzheimer’s is a uniquely human condition, and we do our best to model it in mice. There is no guarantee that what works in mice is what works in people,” he noted.
For those at risk of Alzheimer’s, if this treatment becomes approved, Pieper recommends starting as early as possible. “As soon as you knew you were at risk for Alzheimer’s disease, it would probably make sense to start taking this because we think our models indicate that the brain is constantly fighting off this condition and eventually succumbs to it. The earlier you can start treatment, the better,” he advised.
In the meantime, Pieper encourages people to adopt lifestyle changes that promote brain health. He mentioned several evidence-based strategies to enhance brain resilience, including adequate sleep, following a Mediterranean or MIND diet, managing blood pressure, engaging in moderate physical activity, and maintaining social connections. “It’s critically important that we all control our blood pressure within the normal range,” he stated, highlighting the impact of high blood pressure on the blood-brain barrier.
The effects of Alzheimer’s extend beyond the patient, impacting caregivers significantly. Pieper emphasized the importance of caregivers taking care of their own health as well. He recommended resources such as Hilarity for Charity, an organization founded by comedian Seth Rogen, which provides support for caregivers.
This research represents a pivotal shift in the understanding and treatment of Alzheimer’s disease. Pieper remarked, “This is the first time anybody’s ever shown that the brain can recover from an advanced dementia-like disease. We’re really excited about what we found and there are other people also working on different things as well.”
