As I write this in March of 2015, there are 1,315 registered clinical studies of potential interventions for Alzheimer’s disease (see ClinicalTrials.gov). While it is hard to define clearly, many of these studies deal with nursing issues, rather than medical interventions aimed at preventing or curing the pathology itself. Of those that are testing potential medical interventions, the huge majority of the interventional compounds have beta amyloid as their primary target, while a very small minority have tau protein as their target. In all cases, such interventional studies have been disappointing until now and — given their assumptions — will continue to prove disappointing. Enormous amounts of money is still being funneled into fruitless clinical trial, based on fundamental misconceptions about the pathology of Alzheimer’s and about cell aging in general.
We use 21st century methods to test 19th century concepts.
Consider an apt parallel in how we once thought of other diseases, such as polio in the late 1940’s. A careful review of the medical literature of those days, much of it still on paper rather than electronic, is revealing.
Before the Salk vaccine, there was an almost universally pessimistic (an often unspoken) assumption that polio must be accepted. The question wasn’t one of cure, but of care. The most we could do was to improve iron lungs, leg braces, and nursing care. The medical literature addressed ways to improve pulmonary care for those in iron lungs and medical economists fretted over the likely future costs of long-term nursing care for polio victims. Few people, among them Jonas Salk, believed that the disease might ever be prevented or cured. Most people were wrong: polio is now rare.
More than half a century later, there is an almost universally pessimistic (and often unspoken) assumption that dementia is inevitable. The question isn’t one of cure, but of care. The most we can do is perhaps slow the inevitable decline, marginally improve memory, and provide better nursing care. The medical literature is full of ways to address beta amyloid deposition and medical economists fret over the likely future costs of nursing home care for Alzheimer’s patients. Few people truly believe that Alzheimer’s can be prevented or cured. Most people are wrong: Alzheimer’s may be prevented and cured.
The assumption that the best we ever can do is slow the inexorable decline of Alzheimer’s is based on a misconception about how cell aging — and Alzheimer’s disease — works. Both the logic of the pathology and a growing literature support the etiology of Alzheimer’s disease and other central neurodegenerative “diseases of aging” as beginning not in the neuron, but in the microglial. These cells show early cell aging prior to the clinical diagnosis of degenerative disease. The ability of microglia to clear beta amyloid declines, as does the general ability to support normal neuron function, and the result is gradual neuronal dysfunction and neuronal loss. Therapeutic interventions aimed at beta amyloid, tau protein, or the neuron itself, are missing the target. Such clinical trials will continue to be – predictably — disappointing. Aiming at beta amyloid protein and dying neurons can no more cure Alzheimer’s disease than we can cure polio with leg exercises and iron lungs. If we want to prevent and cure the disease, we must address the pathology where it begins, not in the cells that are mere innocent bystanders.
Over the next few years, it is our intend to show that we can both prevent and cure Alzheimer’s disease by running human trials that will reset gene expression and undercut the basic pathology of Alzheimer’s disease.
We invite your support.