Combination Therapy and Precision Medicine Spotlighted as the Gold Standard for the Next Generation of Alzheimer’s Treatments in the Journal of Prevention of Alzheimer’s Disease (JPAD)

The Publication Features Leading Body of Research Led by ADDF Scientists Based on a Biology of Aging and Geroscience Approach

NEW YORK – January 16, 2024 – The Journal of Prevention of Alzheimer’s Disease (JPAD) with the support of the Alzheimer’s Drug Discovery Foundation (ADDF) recently published a comprehensive issue, “The Biology of Aging: Leading The Next Generation of Alzheimer’s Drug Development With a Geroscience Focus,” which supports the consensus that combination therapy and precision medicine are the future of Alzheimer's treatment. This landmark publication arrives at a critical time in the Alzheimer’s research field following significant drug breakthroughs of anti-amyloid therapies and the emergence of the biology of aging as the leading approach for drug development. This issue emphasizes the need to advance new therapies that target the underlying biology of the disease while also offering a roadmap for the next generation of Alzheimer’s therapies.

“Alzheimer’s will eventually be treated through a precision medicine and combination therapy approach that can be tailored to patients based on their individual biomarker profiles, which has proven to be successful in cancer and other diseases of chronic aging,” says Howard Fillit, MD, Co-Founder and Chief Science Officer of the ADDF. “Aging is the leading risk factor for Alzheimer’s, and the current drug pipeline—where nearly 75% of drugs are exploring novel targets—is a testament to the many years of research, illustrating our understanding of the biology of aging and the potential it presents for uncovering new treatments.”

The special issue showcases seven critical aging pathways and corresponding therapeutics in development that are led by the ADDF-funded investigators—including vascular dysfunction, autophagy, oxidative stress, neuroinflammation, neuroprotection, mitochondrial and metabolic dysfunction, and cellular senescence—all of which have been scientifically proven to contribute to the onset of Alzheimer’s. Each of these novel targets introduces a new and much-needed multi-pronged approach for developing Alzheimer’s treatments, which can complement anti-amyloid drugs on the market. 

The 2023 clinical trials report authored by Jeffrey Cummings, MD, ScD, Joy Chambers-Grundy Professor of Brain Science, and Co-Director of the Alzheimer’s Disease and Related Disorders Innovation Incubator (INNOVATOR) and Department of Brain Health at the School of Integrated Health Sciences at the University of Nevada, Las Vegas (UNLV), chronicles the 187 clinical trials of the 141 unique drugs in development, demonstrating the vast growth and expansion of the Alzheimer’s drug pipeline throughout the last decade.  

“In witnessing the incredible transformation of the Alzheimer's therapeutic field, we are at the brink of a new era,” notes Dr. Cummings. “The advancements we are seeing will undoubtedly shape the next generation of drugs, paving the way for the creation of an arsenal of treatments that will be optimized with biomarker testing to ensure patients are matched with the drugs they need the most. The development of future therapies will enhance our growing understanding of the disease and how the various pathways interact to affect the disease state.” 

This issue offers one of the first and most comprehensive reviews on the role of biomarkers for Alzheimer’s, highlighting the necessity of biomarkers for drug development. Biomarkers allow for more targeted clinical trial participant recruitment, improved treatment monitoring, and help provide the framework for a more rigorous trial design. The value of biomarkers is reflected in the recent approval of anti-amyloid drug Leqembi, which was made possible with the use of biomarker data from the Amyvid® PET scan that received early seed funding from the ADDF. As the field moves towards a broader, multi-faceted approach for developing new treatments, there is a pressing need to validate and develop corresponding biomarkers for each of the critical aging pathways.

The development of multiple novel biomarkers will also be critical to enabling precision medicine by providing the ability to target several modifiable Alzheimer’s risk factors and intervene to prevent the disease. Miia Kivipelto, MD, PhD, Professor of Clinical Geriatrics at Karolinska Institutet, Scientific Founder and Medical and Scientific Director at the FINGERS Brain Health Institute (FBHI), and ADDF board member, outlines her work with the landmark FINGERS trial in this issue, which found that up to 40% of dementia cases can be prevented through lifestyle interventions. This supports the potential benefit of combining lifestyle modifications with novel therapeutics. There is a growing consensus among researchers and clinicians in the Alzheimer’s research space that pairing biomarkers and prevention with new treatments will be instrumental in achieving the ultimate goal to halt progression of the disease. 

“Casting a spotlight on geroscience, this issue of the JPAD not only presents groundbreaking research, but also provides insight towards new avenues in Alzheimer’s prevention,” adds Bruno Vellas, MD, PhD, President and Founder of IHU HealthAge, and Chair of the Department of Internal Medicine & Geriatric at the Alzheimer Disease Research and Clinical Center at Toulouse University Hospital. “This is a noteworthy achievement, as the publication will serve as the first extensive roadmap of non-amyloid pathways with the potential to address the complexity of Alzheimer’s disease.”