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Originally Posted On: https://www.quantum-corp.com/alzheimers-inflammation

 

At A Glance:

• 71% Of Caregivers Are Interested In A Drug Targeting Inflammation

• Caregivers Assume Multiple Inflammation Drugs Are In the Works—They’re Wrong

• 2 in 5 Caregivers Believe Inflammation is the Root Cause Of Alzheimer’s

 

What is Alzheimer’s?

Alzheimer’s is a progressive brain disease that causes a decline in memory, thinking, learning and organization skills over time. Inevitably, it affects a person’s ability to carry out essential daily activities. The disease is historically believed to be caused by an abnormal build-up of tau and beta-amyloid proteins in the brain which cause cells to die. This results in the formation of larger masses called plaques.

Targeting The Fundamental Pathophysiology Of Alzheimer’s

On January 6th, 2023, the FDA approved lecanemab (brand name Leqembi) for the treatment of Alzheimer’s disease. This is the second drug they have approved within the last two years. These new drugs focus on slowing cognitive decline rather than temporarily aiding in relieving symptoms.

Lecanemab was approved using the Accelerated Approval pathway. It is a “humanized monoclonal antibody” that targets amyloid protofibrils for treating early Alzheimer’s. These protofibrils are elongated clusters of cells that grow into a fibril. The results have shown the drug to slow cognitive and functional decline moderately in early-stage cases.

Lecanemab, Buntanetap, ANAVEX®2-73, and Simufilam are just a fraction of the drugs moving along in the current clinical trials.

In January 2023, we surveyed caregivers of Alzheimer’s patients on the newly approved drug lecanemab, and the alternative, anti-inflammatory drug trials conducted by BioVie utilizing its molecule, NE3107. We also asked caregivers about their knowledge of inflammation and insulin resistance in Alzheimer’s.

 

2 in 5 Caregivers Believe Inflammation Is A Root Cause In Alzheimer’s

​In our survey, 63% of Alzheimer’s caregivers have heard of the link between inflammation and insulin resistance and the development of Alzheimer’s Disease. This is expected, as over 11,000 papers on PubMed reference both Alzheimer’s Disease and inflammation. Studies show many factors trigger the production of tumor necrosis factor α (TNFα), considered the master regulator of inflammation in the body. When the body produces TNFα, it further produces various inflammatory factors, the precursors to amyloids, p-tau, and others. This production creates an inflammatory cycle leading to further inflammation, exacerbating disease pathology. TNFα also leads to insulin resistance.

More than half of caregivers have heard of the link between inflammation and insulin resistance with Alzheimer’s. Specifically, 72% of professional caregivers have heard of this linkage and 61% of those caring for loved ones said the same. Those caring for loved ones (43%) and professional caregivers (72%) also believe inflammation is the root cause. However, 33% of those caring for loved ones don’t know if they believe it is a root cause, despite having heard of the link.

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“There are multiple genes that are thought to be associated with the development of Alzheimer’s, but these are “risk” genes. They do not guarantee that someone will develop the disease. Some of these genes are related to inflammatory processes. Managing blood pressure, blood sugar, good diet, exercise, social interactions, etc, may have a role in managing genetic risk.”

— Dr. Joseph Palumbo, Chief Medical Officer, BioVie

Caregivers Assume Multiple Inflammation Drugs Are In the Works—They’re Wrong

Our survey shows nearly half of caregivers (43%) would guess there are at least 3-4 drugs targeting inflammation with 16% of respondents guessing that there are 5 or more of these drugs in development. This, however, is wrong. According to an article by Jeffrey Cummings that looked at all Alzheimer’s clinical trials underway as of January 2022, of 31 Alzheimer’s agents in Phase 3, NE3107 is the only drug candidate addressing inflammation.

Alzheimer’s Drug Development Pipeline

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“Proponents of the amyloid hypothesis might hold that inflammation is caused, primarily, by the plaques and tangles seen in the Alzheimer’s form of dementia, Advances in science suggest that multiple potential causes of dementia exist, and that inflammatory processes may facilitate the development of plaques and tangles in the brain, with there being some evidence that amyloid deposition is part of the brain’s natural defense against inflammation.”

— Dr. Joseph Palumbo, Chief Medical Officer, BioVie

​Despite lecanemab being recently approved, many caregivers (55%) have not heard of it. Of the 45% who have heard of lecanemab, 41% believe it will be somewhat effective in reversing the cognitive decline among those they care for. In comparison, 26% are neutral and 24% believe it will be very effective. Those who believe lecanemab will be somewhat effective also believe inflammation is the root cause at 52%. Forty-four percent are also interested in a drug targeting inflammation.

BioVie, Inc’s Chief Social Impact Officer, Sarah Hoit who was not only a caregiver for her husband who she recently lost to the disease, but over the last 15 years has worked with thousands of families/ caregivers and people with the disease.

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“This is a sea change moment of real hope in the industry where for the first time in 100 years we have multiple drugs on the market with promise, including the hopeful early results of BioVie’s NE3107 molecule that focuses on inflammation. We also believe that getting information out to people about ‘what we know and what we can do about it’ now is critical.”

— Sarah Hoit, Chief Social Impact Officer, BioVie

Through Sarah and BioVie’s non-profit work with “Social Impact Partners” we are starting a speaker series that focuses on what we know and where caregivers and those with the disease can get more information.

71% Of Caregivers Interested in Alzheimer’s Drug Targeting Inflammation

Caregivers with knowledge of inflammation and Alzheimer’s are interested in a drug targeting inflammation with 45% selecting this option. However, 54% have not heard of the clinical trials for NE3107. NE3107 is an oral drug that shown to decrease inflammation and to improve insulin function.” In comparison, 53% of professional caregivers have heard of NE3107 whereas 74% of those caring for family members or loved ones have not.

BioVie is studying inflammation as the root cause of the development and progression of Alzheimer’s. This is a different approach than the other drugs in Phase 3 of clinical trials.

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“BioVie’s is conducting clinical trials examining NE3107 in people diagnosed with Alzheimer’s Disease based on the hypothesis that selective modulation of TNFα production leads to reduction of inflammation and insulin resistance. We believe this triggers a series of processes that leads to healthier neurons, which may be able to improve memory and thinking, and may protect against neurodegeneration.”

— Cuong Do, CEO, BioVie

According to the survey, 71% of caregivers are interested in a drug with BioVie’s approach, with 32% aware that BioVie is developing NE3107 for this purpose.

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“Consumers can compare prescription medications and other natural agents that have effects on TNF-alpha. In a recent review of the effects of these agents, there appears to be evidence to support their potential benefit in dementia.  Unlike these first generation TNF agents, NE3107 seems not to be immunosuppressive.”

— Dr. Joseph Palumbo, Chief Medical Officer, BioVie

Delaying Neurodegenerative Diseases And Reversing Biological Aging

Scientists are also looking at the potential for delaying or reversing biological aging by targeting several diseases, such as neurodegenerative diseases like Alzheimer’s and Parkinson’s. This would also include diseases including heart failure and cancer.

Nir Barziali, director of the Institute for Aging Research, has put his focus on metformin and its possibilities of expanding lifespan. Metformin is primarily used for the treatment of type 2 diabetes by helping to control the amount of glucose (sugar) in the blood. It decreases the amount of glucose you absorb from food as well as the amount made by your liver. It also has positive effects on insulin resistance. Nir Baziali’s metformin efforts don’t stop there, he hopes to also show the drug delays an array of diseases, such as dementia, stroke, etc.

Many other researchers are looking at metformin for its potential to reduce the incidence of neurodegenerative diseases. Scientists have a plan in place to see if metformin prevents or delays major age-related illnesses. Some of these scientists are already taking metformin daily according to this article by National Geographic. However, no clinical trial has demonstrated the impact of metformin on the aging process.

Aging has been shown to be “epigenetic” in nature, whereby our behavior (on things such as diet and exercise) and environment interact with our genetic code to affect the aging process. Inflammation has been shown to accelerate the aging process, and thus has been associated with many age-related disorders.

BioVie’s Phase 2 data showed that 19 of 22 participants patients treated with NE3107 for three months saw a reversal of their biological clock. This does not mean that the drug can make us younger. It means that NE3107 may have an epigenetic impact and thus could play a role in reducing the burden of disease as we all age. BioVie is starting to work with collaborators to explore additional age-related diseases where NE3107 could help. If successful, this could help us live healthier as we live longer.

Scientists continue to look at chronic inflammation, which they estimate is a major factor in more than half of all deaths worldwide. Even research on cellular reprogramming is taking a shot at reversing aging and eliminating the illnesses that come with it. However, cellular reprogramming research is still very new and scientists are unsure of what it will do for humans. Researchers at the Harvard T.H. Chan School of Public Health say there are still things we can do to try to delay aging.

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“It is not known just yet, but a common sense approach would suggest that exercise, management of blood pressure and blood sugar, good sleep, and an overall healthy lifestyle would be helpful.”

— Dr. Joseph Palumbo, Chief Medical Officer, BioVie

As work continues on delaying aging, researchers have found 5 habits that may help in the meantime. A good diet, regular exercise, healthy weight, not smoking, and not drinking too much all have an effect on aging. Research shows it “may increase life expectancy by 14 years in women and 12 years in men.” Though you should aim to achieve all 5 habits, Matt Kaeberlein, professor of laboratory medicine and pathology says that exercise will give you the “best bang for your buck.”

All data in this report was collected using the online survey platform, Pollfish, and commissioned by Quantum Research Group in partnership with Brand Boba. A total of 1,000 American caregivers for Alzheimer’s patients were included according to Pollfish’s algorithm and screening methodology, with a 95% confidence level and a margin of error of 3% on the total US population. Results for individual states will vary. The survey was conducted on January 25, 2023. All respondents were asked to answer all questions truthfully and to the best of their abilities.

For full survey data or to interview one of our experts,

please email [email protected].

* BioVie Inc. is a client of Quantum Research Group, LLC.