PHARMACEUTICAL INTERVENTIONS FOR AGE-ASSOCIATED DISORDERS
As discussed in the essay entitled “The Current Paradigm and Age-Associated Disorders,” under the current aging paradigm, the medical establishment tends to treat age-associated degenerative diseases in much the same manner that it approaches infectious diseases. This essay will discuss the role of pharmaceutical interventions.
Pharmaceutical interventions have proven to be quite successful when the goal is preventing or curing an infectious disease. That’s because such interventions are targeted at the invading pathogens that are known to cause the disease. An effective vaccine can prevent diseases by conditioning the immune system to recognize and attack the pathogen before it can gain a foothold. Antibiotics can help bring about a cure by assisting the body’s immune system in destroying pathogens that have successfully invaded the subject.
Drugs that are intended to treat degenerative disorders cannot do so by warding off or attacking any invading organism, so neither the vaccine nor antibiotic approach has any applicability. Instead, the pharmaceutical industry has substituted an approach that typically involves disrupting some physiological process that is associated with a disease. This approach has had some success with various forms of cancer. However, although often identified as an “age-associated disease,” cancer is not directly caused by FDS. The problem with attempting to disrupt the FDS process is that there is no process that can be disrupted. FDS is not the result of any mechanism attacking any organ or system. The only thing that is going on is that intrinsic damage is accumulating over time. And the cause of that accumulation is that the maintenance system is not doing an adequate job of removing and replacing components that have become defective as a result of intrinsic damage.
Drugs are governed by the Food and Drug Administration (FDA), which is tasked with making an affirmative substantive finding that a drug is “safe and effective” before approving the drug for sale to the public. A drug that is intended to treat an infectious disease typically attacks the underlying causative pathogen in some fashion. Thus the determination of whether it is safe and effective is relatively straightforward. If studies shows that subjects who took the drug recovered from the disease substantially more quickly than subjects who didn’t take the drug, it is probable the drug really did do something to trip up the bug. Since the drug is targeted at the bug, rather than the body or its metabolic processes, the side effects should appear relatively quickly and be obvious. Also, since these drugs are designed to cure a disease, they are typically prescribed in a treatment regimen that lasts days or weeks rather than years.
As it relates to age-associated degenerative disorders, the drug development process typically involves identifying some substance that will interfere with a natural physiological process. The drug developer then concocts a reason why interfering with that process has a positive effect on some risk factor, bio-marker or symptom associated with a degenerative disease. There are numerous drugs that target various risk factors by, say, lowering blood pressure or interfering with cholesterol formation. Many of these drugs, statins for example, have proven to be remarkably successful from a financial standpoint. But none of them are attacking the actual cause of any disease. With the billions of dollars that are at issue, it is no surprise that the pharmaceutical companies are able to fabricate studies that establish a statistical correlation that provides sufficient grounds to enable the FDA to approve such a pharmaceutical intervention. But obtaining FDA approval is not the same as establishing, as an objective scientific fact, that an intervention has any real connection to the cause of any age-associated degenerative disease.
The biological processes that these drugs disrupt are the result of hundreds of thousands of years of natural selection. So negative side effects are inevitable. Moreover many of the drugs currently on the market have been created solely for the purpose of counteracting adverse effects of other drugs. The result is that a typical adult who is suffering from FDS ends up taking a variety of drugs, many of which are very expensive, and none of which have a material effect on the actual disorder. The pharmaceutical companies are very profitable, but in all cases the symptoms of FDS continue to worsen over time until the subject inevitably dies.
Alzheimer's Disease
A specific example of how the pharmaceutical companies are able to develop and market pharmaceutical interventions that are enormously profitable, but provide a limited benefit to patients and to the health care system at large, is the relatively recent FDA approvals of a pair of drugs that are designed to treat Alzheimer’s Disease. Alzheimer’s Disease is the predominant type of dementia.
There is no doubt that Alzheimer’s Disease, which is just one of the age-associated degenerative disorders, places an enormous financial burden on the United States. “In 2022, the estimated healthcare costs associated with AD treatment were $321 billion, with costs projected to exceed $1 trillion by 2050. These cost-of-care projections are based on direct healthcare costs and are likely underestimated because indirect costs associated with AD treatment are usually not included. Indirect costs such as loss in productivity, diminished quality of life, and an increasing dependence on informal unpaid care provided by family caregivers augments the economic and societal burden of this disease.”¹
According to the Alzheimer’s Association, in 2022 over 11 million Americans were providing unpaid care for a family member or friend with dementia at a societal cost of an additional $340 billion.² The persons who provide that care frequently have their own health issues arising from the stress associated with providing care to someone in cognitive decline. Note that these cost estimates are based on the estimated 6.7 million Americans currently suffering from Alzheimer’s dementia. That number is expected to double by 2050. As noted above, by 2050, the annual direct healthcare costs for treating Alzheimer’s dementia are projected to exceed $1 trillion.
Under the current aging paradigm, the progressive declines in brain functionality experienced by substantially all humans with advancing chronological age – e.g., slower thinking, occasional problems remembering things – is a normal part of a natural human aging process. Alzheimer’s Disease is treated as an aberration that occurs in only some humans late in life. Alzheimer’s Dementia is labeled a different type of dementia because it is characterized by the appearance of amyloid plaques, which are clumps of protein that accumulate in the brain. There is an unproven hypothesis that it is the amyloid plaques that are the actual cause of the cognitive decline.
The FDA has now approved two drugs that target the amyloid plaques. The first was Aducanumab (marketed by Biogen under the name Aduhelm). Aduhelm was approved under a program called “accelerated approval,” which allows the authorization of drugs without persuasive proof of benefit if they are for serious diseases with few treatment options and if the drug affects part of the disease’s biology (known as a biomarker) in a way that is “reasonably likely to predict clinical benefit.” In this case the biomarker was the amyloid plaques.
Although Biogen’s two major clinical studies did show that Aduhelm reduced the amyloid plaques in the test subjects, the studies were so inconclusive with respect to the issue of whether the drug slowed cognitive decline that both were aborted.3 After the studies were called off, Biogen was able to come up with data from one of the two studies that Biogen argued was statistical proof that high doses of Aduhelm did cause short-term improvement in cognitive ability in certain early-stage cases of Alzheimer’s Disease. The other study showed no benefit to any cohort of subjects at any dosage level. Both studies showed that the drug had potentially dangerous side effects. Ultimately, in a very controversial decision, the FDA approved the use of Aduhelm.
Among the reasons cited for the FDA’s controversial decision is that patient groups are desperate for anything that might mitigate the effects of such a horrible disease. Some argue that even false hope is better than no hope at all. Biogen originally priced Aduhelm at $56,000 per year; it lowered the price by half at the end of 2021. Regardless, the FDA’s approval of the drug provided a huge financial windfall for Biogen. So, of course, other pharmaceutical companies have followed the path of developing drugs that attack amyloid plaques, even though there is no proof that eliminating plaques has a material beneficial effect on cognitive decline.
In January of 2023 the FDA approved a second drug, Leqembi, which also attacks amyloid plaques, through its fast-track process. In July of 2023, the agency granted the drug full approval, which means it can be covered by Medicare subject to certain conditions. No one suggests that either of the approved drugs, nor any other drug that attacks amyloid plaques, will ever prevent or cure Alzheimer’s Disease. The sales pitch is that, when given to patients with early-stage Alzheimer’s, who are also provided with other interventions that ease the symptoms of Alzheimer’s, the symptoms of the subject patients may not progress as quickly as those with no interventions.
Like all drugs that the pharmaceutical industry has created for age-associated degenerative diseases, there are significant negative side effects. According to the National Council on Aging, the most common side effects of Leqembi are “bleeding in the brain that usually goes away over time. Some people may have symptoms such as headache, confusion, dizziness, vision changes, nausea, and seizure that occur with the swelling and bleeding. Other side effects include nausea, vomiting, and changes in blood pressure.”
The pharmaceutical industry has trumpeted the approval of these two drugs as a great breakthrough. Now that the FDA has approved of the approach of attacking amyloid plaques as a treatment for Alzheimer’s Disease, other pharmaceutical companies are also attempting to develop drugs that use that approach.
What’s wrong with the pharmaceutical industry’s focus on attacking amyloid plaques? First, the treatments are quite expensive. Eiasi, Leqembi’s manufacturer, set its list price at $26,500 per year. That’s for administering the drug itself. Additional costs include periodic medical visits and required regular brain scans. And users of Leqembi are expected to continue to receive the other interventions that are intended to slow the rate of cognitive decline. The bottom line is that the costs associated with Aduhelm and Leqembi (and the other amyloid attacking drugs to come) are all added costs. Since they neither prevent nor cure the disease these drugs will do nothing to reduce the enormous financial burden Alzheimer’s dementia imposes on society. They will only add to that burden.
The more insidious problem is that that the pharmaceutical companies now have a proven strategy for generating enormous profits off of the dementia crisis. Simply develop additional drugs that attack amyloid plaques.³ As a result, there is little financial incentive for the pharmaceutical industry to undertake the financial risks associated with developing interventions that would actually attack the underlying cause of the disorder. Besides, under the current aging paradigm, the cause of dementia, if there is one, is the slow accumulation of intrinsic damage which is assumed to be a normal part of a natural human aging process.
The Approach to Alzheimer's Disease Indicated by the New Paradigm
Under the New Paradigm, substantially all forms of dementia, including Alzheimer’s Disease, are degenerative disorders. Degenerative disorders are caused by an environmental factor interfering with the proper functioning of the maintenance system.
Scientists have provided us with an abundance of evidence that humans do have a “brain remodeling” process. Klotho, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and a variety of neural transmitters are just a small sampling of the substances that scientists have identified as being associated with maintenance of the brain and the central nervous system. Under the current aging paradigm, each such substance is studied in isolation. Older persons do tend to have lower concentrations of such substances in their blood. However, unlike a nutritional deficiency which typically can be remedied by ingesting the single item that is missing from the diet, the New Paradigm suggests that the reason that humans appear to have insufficient supplies of these substances circulating in their bloodstreams is that the substances are secreted into the blood only when necessary to support the brain remodeling process. Some environmental agent (or absence thereof) is interfering with the process itself, thus resulting in low blood concentrations of all of the substances.
An example of the futility of trying to duplicate a maintenance process by supplementing one or more of the substances in isolation is the failure of the experimental drug idalopirdine. Scientists had noted that people suffering from Alzheimer’s Disease typically demonstrated low levels of neural transmitters. Idalopirdine was designed to increase supplies primarily of the neural transmitter serotonin, but also four other neural transmitters that are associated with Alzheimer’s Disease: glutamate, norepinephrine, acetylcholine and dopamine. Although billions of dollars were spent in developing and testing the drug, the pharmaceutical company was unable to demonstrate that it was effective in treating Alzheimer’s Disease.
The New Paradigm suggests a different path. The reason that the brain remodeling process is not sufficiently effective to ward off dementia in a large number of humans is not that the substances are not being produced by the endocrine system, but rather that some environmental agent (or the absence thereof) is interfering with the brain remodeling maintenance process. The solution is not to try to duplicate the process, but rather to identify and neutralize the environmental agent, thus allowing the process to function in the way it was designed.
- Skaria AP,The Economic and Societal Burden of Alzheimer Disease: Managed Care Considerations, AJMC (2022).
- Alzheimer’s Association. 2023 Alzheimer’s Disease Facts and Figures. Found on the internet at:
- According to the National Council on Aging, “there are nearly 200 Alzheimer’s drugs in active clinical trials. Most, like Aduhelm, represent disease-modifying agents…”