By Dr. Greg Jicha,
University of Kentucky Sanders-Brown Center on Aging
This is the dawn of disease-modifying therapies for Alzheimer’s disease, and a cure is on the horizon. This message of hope reverberates in the hearts of people affected by Alzheimer’s disease and their loved ones, giving them a sense that they can fight this disease that was once seen as a losing battle.
Decades of basic science research have begun to unlock the mysteries of Alzheimer’s disease. Like the pieces of a puzzle coming together, gradually forming a picture, researchers worldwide have been assembling the pieces of the Alzheimer’s puzzle. While not yet complete, a picture has emerged that reveals key targets for intervention that are being developed on a global scale.
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Alzheimer’s disease represents a complex interplay between the buildup of toxic proteins and brain cell death that leads to the progressive memory loss characteristic of this disease. Amyloid plaques and neurofibrillary tangles, the characteristic pathological features of Alzheimer’s disease, are formed from abnormal proteins in the brain that may lead to cell death and dysfunction. Inflammation and oxidative stress (“brain rust”) are part of the picture, again leading to the loss of brain cells necessary for normal memory and thinking.
Our understanding of these processes has identified multiple targets for the development of experimental therapies designed to stop Alzheimer’s disease in its tracks. Anti-amyloid strategies hope to prevent the buildup of or even remove toxic amyloid plaques from the brains of persons with Alzheimer’s disease. Other strategies rely on preventing the formation of neurofibrillary tangles. Still others are focused on reducing inflammation and oxidative stress.
While seemingly disparate strategies, they all share two things in common, they directly target the disease process in Alzheimer’s disease and they all stand the chance of slowing or even stopping this devastating disease. Researchers across the globe, including me and others at UK, are currently testing dozens of such experimental therapies in persons with Alzheimer's disease today. Here are just a few:
• Bapineuzimab is a genetically engineered antibody that targets toxic amyloid, potentially removing it from the brain. http://www.icarastudy.com/
• Naturally occurring anti-Alzheimer’s antibodies are produced by some people resistant to the disease and these are also being used as a potential therapy for those who don’t make such potentially protective antibodies. http://www.gapstudy.com/
• Dimebon targets mitochondria (the brain’s batteries), hopefully preventing cellular corrosion and brain cell death. http://www.medivation.com/product-pipeline/dimebon
• Souvenaid is a medical food that may help the brain regenerate new connections between nerve cells that may help slow or circumvent the memory loss caused by Alzheimer’s disease. http://www.souvenaid.com/
Which therapy, if any, will prove to be a cure is unknown. Will a cure be found this year, five years from now, or longer? Again, the answer is unknown. Recent failures of disease-modifying therapies targeting amyloid, including Alzhemed and Flurizan, have not slowed enthusiasm for dozens of compounds currently coming into clinical trials for Alzheimer’s disease.
Reaching our ultimate goal -- finding a cure -- is critically dependent on perseverance, ingenuity, commitment, and our ability to unite researchers, clinicians, and persons affected by Alzheimer’s disease as a global community in this struggle.
Dr. Greg Jicha is assistant professor of neurology, UK College of Medicine and UK Sanders-Brown Center on Aging and Alzheimer's Disease Center.