It Is Lifestyle Related and a Drug Will Not Fix It
In what has become an all too familiar story, another drug trial failed to produce any important benefit. Genentech recently announced that the phase II trial of their drug semorinemab failed to produce any measurable clinical effect in slowing the decline in cognitive function in Alzheimer’s patients. The trial treated 457 participants across 97 study centers failed to achieve the trial’s primary outcome benefit on 3 different cognitive function tests to assess slowing of decline compared to a placebo.
The study showed that the drug did meet the secondary outcome measure generating no increased adverse effects compared to the placebo. This second objective is relatively meaningless. If the drug produces no benefit, the concern about adverse effects seems a non-issue as the drug will not be approved for use. As Queen sang back in 1980, “Another one bites the dust”.
To date, there have been approximately 250 drug trials for Alzheimer’s disease. Only 2 drug classes have been approved from these trials, but their benefit is limited. They soften the symptoms of the disease for a relatively short interval but do not slow the eventual outcome.
At the same time, 2 clinical trials of non-drug therapies did produce some positive results in preventing the disease. The CHAP and MAP trials look at the adherence to 5 healthy lifestyle practices and the ability of adherence to lessen the rate of those developing the disease. These factors included not smoking, following a Mediterranean dietary pattern, regular moderate exercise, light to moderate alcohol intake, and engagement in regular cognitive activity. The 2 studies followed over 600 older adults for 6 years.
Subjects in these studies were separated into 4 groups; those following 0-1, 2-3, or 4-5 of these healthy lifestyle behaviors. Those who transitioned to Alzheimer’s disease over that interval in each group were compared. Those following 2-3 healthy lifestyle behaviors had a 37% lower rate of the disease compared to the group following 0-1. Those following 4-5 had a striking 60% reduction in the rate of developing the disease.
Beginning a preventative lifestyle program in midlife or before is important. That approach however, does not apply to those who already are struggling with the disease. A more comprehensive lifestyle program, The Bredesen Protocol , has stepped in to fill that need. The program was developed by a leading neuroscience and Alzheimer’s researcher, Dale Bredesen, M.D. It has shown good success at bringing patients back from different stages of this disease which is now the third leading cause of death.
As Dr. Bredesen states, Alzheimer’s disease is not as much a brain disease as it is a brain manifestation of broader systemic imbalances that lead to cell degeneration and death. These new lifestyle modification trials seem to agree with that conclusion.
Alzheimer’s is a complex disease which causes the brain to build up two toxic proteins, beta amyloid and P Tau. The different drugs are designed to remove one of these proteins. They do not address the underlying mechanism of what is causing the brain to make these proteins. If metabolic imbalances that drive the production of these proteins is not resolved, the brain is making more as the older ones are removed. That is like adding water to a bucket that has an equal size hole in it where it is running out.
SEMORINEMAB: ANTI-TAU DRUG FAILS PHASE II CLINICAL TRIAL FOR EARLY ALZHEIMER’S DISEASE. Neuro Central, 24 SEP 2020.
Dhana et al. HEALTHY LIFESTYLE AND THE RISK OF ALZHEIMER DEMENTIA: FINDINGS FROM 2 LONGITUDINAL STUDIES. Neurology, July 28, 2020; 95 (4).