CLEVELAND – For over a century, Alzheimer’s disease (AD) has been considered irreversible, with research primarily focusing on prevention or slowing its progression. However, a groundbreaking study from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center has challenged this notion by suggesting that the disease could potentially be reversed, at least in animal models.
The study, led by Kalyani Chaubey, PhD, from the Pieper Laboratory, and published in Cell Reports Medicine, reveals that maintaining or restoring the brain’s balance of NAD+, a central cellular energy molecule, can not only prevent but also reverse Alzheimer’s disease in mice. This finding could pave the way for new therapeutic approaches aimed at recovery rather than just management of the disease.
Understanding the Role of NAD+ in Alzheimer’s
NAD+ levels naturally decline with age across the body, including the brain. This decline is even more pronounced in individuals with Alzheimer’s, leading to cellular dysfunction and the inability to perform critical processes. The research team used mouse models engineered to express genetic mutations that cause Alzheimer’s in humans to study this phenomenon.
These models included mice with mutations in amyloid processing and tau protein, both of which are major factors in the early development of Alzheimer’s. The mice exhibited symptoms similar to those seen in human Alzheimer’s patients, such as cognitive impairments and brain pathology.
Breakthrough Findings
Remarkably, the study demonstrated that by administering a pharmacologic agent known as P7C3-A20, developed in the Pieper lab, researchers could restore NAD+ balance in the brain. This restoration not only prevented the onset of Alzheimer’s in mice but also reversed significant disease progression, allowing for full cognitive recovery.
“Restoring the brain’s energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer’s,” said Andrew A. Pieper, MD, PhD, senior author of the study.
Implications for Human Treatment
The implications of these findings are profound, suggesting a potential paradigm shift in how Alzheimer’s could be treated in the future. Dr. Pieper emphasized the importance of maintaining NAD+ balance without elevating it to levels that could promote cancer, a risk associated with some over-the-counter NAD+ precursors.
Currently, the technology is being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper. The next steps involve moving this therapeutic approach into human clinical trials to determine its efficacy in patients.
Expert Opinions and Future Directions
Dr. Pieper, who also holds prestigious positions at UH and CWRU, highlighted the significance of this research in offering hope to Alzheimer’s patients. “The key takeaway is a message of hope – the effects of Alzheimer’s disease may not be inevitably permanent,” he noted.
Dr. Chaubey added, “Through our study, we demonstrated one drug-based way to accomplish this in animal models, and also identified candidate proteins in the human AD brain that may relate to the ability to reverse AD.”
“This new therapeutic approach to recovery needs to be moved into carefully designed human clinical trials,” Dr. Pieper explained, emphasizing the need for further research to pinpoint critical aspects of brain energy balance and explore complementary approaches.
Looking Ahead
The study’s findings encourage new research into complementary approaches and clinical testing in patients. The potential to reverse Alzheimer’s, even in advanced stages, offers a new frontier in the fight against this debilitating disease. As researchers continue to explore the intricacies of brain energy balance and its role in cognitive health, the hope is to translate these promising results from animal models to human patients, ultimately changing the landscape of Alzheimer’s treatment.
With ongoing research and potential clinical trials on the horizon, the scientific community and Alzheimer’s patients alike eagerly await further developments that could redefine the understanding and treatment of this complex disease.
