We have made very little progress in the treatment of Alzheimer’s Disease. Standard treatments, such as donepezil (Aricept) and memantine (Namenda), accomplish very little with regards to improving quality of life in these unfortunate individuals. Similarly, research and development by the pharmaceutical industry has not yielded any “home runs.” We have spent many years and many dollars developing drugs to target amyloid beta plaques with little success.
Recently, the FDA approved lecanemab (Leqembi) for the treatment of Alzheimer’s disease. The results showed that lecanemab successfully removed amyloid and tau proteins from the brains of people living with early Alzheimer’s disease. For the people taking lecanemab, this meant that the decline in their thinking and memory skills was slowed down by 27%. It also slowed down the decline in quality of life by up to 56%.
Donanemab is the most recent of the immunotherapy drugs targeting amyloid beta, as it successfully leads to the removal of amyloid from the brain. In May 2023, the company reported its Phase III study showed the drug could slow the pace of Alzheimer's disease by 35%. In July 2023, results from 1,736 people treated with donanemab showed slowing of Alzheimer's progression at 76 weeks, with 24% of the people, however, displaying cerebral edema.
Yet, the best we have been able to do is to slow down the rate of cognitive decline; not stop the decline nor reverse it. There are a growing number of scientists that are challenging the buildup of insoluble plaques of beta-amyloid as the cause of Alzheimer’s disease. Many people with amyloid plaques have no symptoms of dementia, and treatments aimed at slowing the buildup of plaques have shown no effect on reversal of the disease process.
So, what is the solution to this problem called Alzheimer’s Disease? What if I substituted Alzheimer's Disease for the word “Cancer;” or substituted any other chronic disease? With chronic diseases, there is typically not a single drug or a single modality that will successfully treat or manage the disorder. The disorder must be treated with multiple modalities.
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Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Increasing evidence also suggests that oxygen therapy may improve many of the aforementioned pathological aspects of AD.
Patients with Alzheimer’s Disease (AD) or mild cognitive impairment (MCI) were treated with HBOT (99.9% O2, 0.4 to 0.7 MPa) for 40 minutes, once per day, for 20 days. Cognitive function and daily living activities were evaluated before HBOT and at 1, 3, and 6 month follow-ups. HBOT ameliorated cognitive impairment in patients with AD patients or amnestic MCI (Chen et al., 2020).
Another study also showed that HBOT (60 daily HBOT sessions within 3 months) increased cerebral blood flow and improved cognitive performance in older adult patients with significant memory loss at baseline (Shapira et al., 2021). Furthermore, HBOT also promoted good cognitive function healthy individuals (Yu et al., 2015).
A study from researchers at Tel Aviv University and Shamir Medical Center showed that HBOT halted the growth of small amyloid beta plaques and reduced the volumes of medium-sized and large plaques, as well as prevented the formation of new ones.
Alzheimer's Management by Albumin Replacement (AMBAR) study: At 14 months, participants in the TPE-treated group vs the placebo group experienced significantly less decline. Importantly, there was a statistically significant improvement in quality of life (QoL) measured by a self-reported questionnaire among patients with mild-AD from baseline to 14 months among the TPE-treated groups compared with the control group. A self-reported improvement was not seen among patients with moderate-AD, although an improvement in QoL was reported by caregivers among this population, perhaps suggesting diminished awareness of cognitive and functional impairments in the moderate-AD group.
Oxidative stress is believed to be an important player in AD pathology. Glutathione (GSH) is a major antioxidant, and it is already known that GSH is depleted significantly in the hippocampal regions in mild cognitive impairment (MCI) and AD patients compared to healthy old subjects. A recent study has shown that the depletion of GSH level in MCI and AD patients in the hippocampal regions is directly correlated with executive function. There is currently an ongoing trial at Baylor College of Medicine using oral glycine and n-acetylcysteine (which are two of the 3 substances necessary for the production of glutathione) for the treatment of patients with AD.
Australian researchers have shown that a dietary supplement that increases the levels of a powerful antioxidant in the brain may represent a novel strategy for the treatment and/or prevention of cognitive impairment and debilitating neurodegenerative diseases such as Alzheimer’s disease. A team of researchers from UNSW Sydney’s Centre for Healthy Brain Ageing (CHeBA), and the School of Biotechnology and Biomolecular Sciences (BABS), has shown that dietary supplementation with glutathione precursor γ-glutamylcysteine (γ-GC), marketed as GlyteineTM, reduced oxidative stress, neuroinflammation and amyloid pathology in the brains of transgenic mice, a murine model to study Alzheimer’s disease. The study also found significant cognitive improvements in the mice as determined using the Morris water maze, a test often used to test memory in mice.
Researchers at RUSH University Medical Center recently discovered that a muscle-building supplement called beta-hydroxy beta-methylbutyrate, also called HMB, may help protect memory, reduce plaques and ultimately help prevent the progression of Alzheimer's disease. Studies in mice with Alzheimer's disease have shown that HMB successfully reduces plaques and increases factors for neuronal growth to protect learning and memory. Previous studies indicate that a family of proteins known as neurotrophic factors are drastically decreased in the brains of people with Alzheimer's disease and have been found to help in survival and function of neurons, which are cells that receive and send messages from the body to the brain and vice versa.
"Our study found that after oral consumption, HMB enters into the brain to increase these beneficial proteins, restore neuronal connections and improve memory and learning in mice with Alzheimer's-like pathology, such as plaques and tangles," Pahan said.
At Institute for Healthy Aging, we are participating in the Expanded Access Program (EAP) for families and patients who would like to try TB006. TB006 is an innovative drug designed to combat Alzheimer's Disease (AD) by targeting Galectin-3 (Gal3). https://www.biospace.com/article/releases/truebinding-granted-type-b-end-of-phase-2-meeting-with-fda-for-discussion-of-accelerated-development-pathway-for-tb006-alzheimer-s-disease-treatment/
At Advanced Medical Therapeutics, we combine multiple modalities to treat AD, including a cocktail of supplements to complement the aforementioned treatments.
