Thirty years ago, cancer and heart disease were the diseases of aging that Americans dreaded the most. People called cancer “The Big C.” In the United States in 1990, the death rate from cancer was 216 per 100,000 population. From that date on, there has been a steady and monotonic decline down to 157.5 per 100,000 population in 2017. There are multiple reasons for this. Many people who took up cigarette smoking in their youth, were dying of lung cancer in 1990.
Many of these were servicemen during World War II who received a few cigarettes along with their food rations every day. Donating free cigarettes to the war effort turned out to be a profitable move by the tobacco companies, after the soldiers and sailors became addicted to nicotine. By 1990, these men (and some women) were close to hitting age 70 and cancer diagnoses had started to rise.
There has been a lot of progress since the 1990s in treating cancers of all types. Many cancers that used to be equivalent to a death sentence are now curable. Major progress has been made in preventing and treating heart disease too. However, there is one disease of aging where progress has been virtually nonexistent. That disease could well be called “The Big A”: Alzheimer’s Disease (AD).
Lack of progress is not due to a lack of trying, and there have been some clues as to what might be causing the epidemic of AD among older people. Despite the clues, there are no effective treatments of AD. This is tragic, because as we make progress against cancer, heart disease, and other diseases, more and more people are living long enough to experience the slow but inexorable mental decline caused by AD.
A hopeful sign appeared recently in the Journal of Experimental Medicine (JEM) titled, Preclinical validation of a potent ϒ-secretase modulator for Alzheimer’s disease prevention.
Wait. Did that paper title use the word “prevention”? If there is any medical intervention that is better than a cure, it is prevention. If you can prevent a disease from occurring in the first place, that is the best outcome. If the intervention can slow or stop the progress of already existing disease, that is a great thing too.
The paper I cited above is a preclinical study. That means that experiments were performed on animals, but not yet on humans. However, the results in the animal studies are encouraging.
What causes AD anyway? That’s a great question, and there are several conditions that are competing as an explanation. Several might play a role in the disease process, with different factors being more important in different people. One thing seems to be highly associated with AD, to the point where it is considered a sure sign of the disease. It is a protein called amyloid-beta (Aβ). When the brains of people who have died of Alzheimer’s disease are analyzed, they are found to be infested with clumps of Aβ called amyloid plaques.
It seems logical to assume that removing amyloid plaques from the brains of Alzheimer’s patients should alleviate the disease, at least to some extent. One class of substances that might eliminate the amyloid plaques is the class of gamma-secretase (ϒ-secretase) inhibitors. Unfortunately, this approach has not worked well due to side effects caused by those ϒ-secretase inhibitors. Apparently, it is not a great idea to just eliminate ϒ-secretase. It is there for a reason.
The JEM paper describes the testing of a ϒ-secretase modulator rather than an inhibitor. This drug, which is called “compound 2” in the paper, reduces the net production of some forms of Aβ (Aβ42 and Aβ40), while enhancing the net production of two other forms (Aβ38 and Aβ37). The neuritic plaques that are characteristic of AD are primarily composed of Aβ42, so selectively reducing those forms of the Aβ protein could reduce the toxicity of the plaques without generating the harmful side effects that occur when generation of all forms of the Aβ protein are inhibited.
This work is promising and deserves aggressive follow-up. The amount of progress against The Big C has been amazing over the past thirty years. Similar progress against The Big A would alleviate a huge amount of human suffering, both of people with AD and with the people who love them.
BIO:
Allen G. Taylor is a 40-year veteran of the computer industry and the author of over 40 books, including Develop Microsoft HoloLens Apps Now, Get Fit with Apple Watch, Cruise for Free, SQL For Dummies, 9th Edition, Crystal Reports 2008 For Dummies, Database Development For Dummies, Access Power Programming with VBA, and SQL All-In-One For Dummies, Third Edition. He lectures internationally on astronomy, databases, innovation, and entrepreneurship. He also teaches database development and Crystal Reports through a leading online education provider. For the latest news on Allen’s activities, check out his blog at wwwallengtaylor.com or contact him at allen.taylor@ieee.org.