Over the years, researchers have learned that chronic inflammation may be to blame in an increasing number of illnesses that were not originally thought to be inflammatory. Of course, inflammation has been implicated in many forms of arthritis and autoimmune diseases.
However, researchers are learning that inflammation may also be to blame in diabetes, heart disease, and even Parkinson’s disease, Alzheimer’s disease, and mental illnesses like depression. In fact, some studies have found that more than half of all deaths today can be attributed to inflammation-related diseases.
Thus, targeting inflammation is becoming an even bigger and bigger market opportunity for biotech companies. According to one estimate, the global anti-inflammatory therapeutics market was worth $99.6 billion in 2021 and is expected to reach $127.5 billion by 2030 – a compound annual growth rate of 4.5% between 2022 and 2030.
Targeting Inflammation In Parkinson’s And Alzheimer’s
On one hand, inflammation is part of the body’s natural defense mechanism as the immune system recognizes and removes whatever is damaging it and then starts the healing process. However, illnesses and chronic conditions occur when inflammation runs out of control and starts damaging the body it was designed to heal and protect.
In the case of Parkinson’s disease, a growing body of evidence suggests inflammation plays a major role in both the development and progression of the disease. A study published just two years ago was one of the first studies to pinpoint inflammation in the blood of Parkinson’s patients in the earliest stage of the disease.
Statistics show the urgency of developing advances in Parkinson’s and Alzheimer’s. In the U.S., 90,000 people are newly diagnosed with Parkinson’s every year, while 1 million currently have the disease.
For Alzheimer’s, more than 6 million Americans have the disease, including one in every nine people age 65 and older. By 2050, the number of Americans with Alzheimer’s is expected to approach 13 million. Deaths from the disease more than doubled between 2000 and 2019.
Cuong Do, president and CEO of biotech firm BioVie, shares the latest on what’s being done to treat these two devastating diseases.
What can you tell us about the importance of targeting inflammation in diseases like Alzheimer’s and Parkinson’s that weren’t traditionally considered inflammatory?
Inflammation is the root of many evils in the body, and we’re just starting to scratch the surface on this discovery. For example, researchers have found that inflammation accelerates the aging process, and of course, we have long known that a person’s odds of developing Alzheimer’s or Parkinson’s increases as they age.
Interestingly, one study found that rheumatoid arthritis patients taking a drug class called TNF (tumor necrosis factor) blockers had a roughly 50% lower chance of developing Alzheimer’s than patients who were not. Since TNF-α is the master regulator of inflammation, blocking it reduces inflammation.
This is only one piece of a rapidly growing puzzle of how inflammation is the key factor in countless diseases, even those in which inflammation isn’t immediately obvious. It’s clear that reducing inflammation in the body could prevent certain diseases, which suggests reducing inflammation in symptomatic patients could bring significant improvements in those symptoms.
How did BioVie decide to target Alzheimer’s and Parkinson’s specifically rather than other disease areas?
I drove BioVie’s acquisition of NE3107, the drug candidate we’re running clinical trials on for Alzheimer’s and Parkinson’s. I personally started researching Alzheimer’s in the late 1990s. I’ve also been a board member at BioVie for quite some time, and I’ve been an investor in the company since the early days.
At that time, the company was focused entirely on liver disease. However, a few years ago, I ran across what I was convinced was the most promising drug candidate to treat Alzheimer’s, which was tagged as NE3107. I joined BioVie to guide the acquisition of that asset, and part of that deal was that I would become CEO, which I came out of retirement to do.
What roles does inflammation play specifically in Parkinson’s and Alzheimer’s?
In the case of Alzheimer’s all the processes in the body that cause inflammation have one thing in common. They activate ERK (extracellular signal-regulated kinase), a central regulator of many cellular processes, including inflammation.
Ultimately, ERK activation then leads to the production of TNF-α, the master regulator of inflammation. The result is an inflammatory cascade that results in increased ß-amyloid, a protein that clumps together in the brain of Alzheimer’s patients to form plaques.
ERK activation also plays a major role in Parkinson’s. In this disease, ERK activation again leads to the production of TNF-α, leading to insulin resistance. Pre-clinical studies have shown that inflammation and the associated insulin resistance are required to develop Parkinson’s symptoms.
What patient goals or outcomes would be considered the gold standard for Parkinson’s and Alzheimer’s treatments?
Improving motor control by a clinically meaningful margin is considered the holy grail in Parkinson’s treatments. In Alzheimer’s, the gold standard for treatment includes improvements in cognitive function, memory loss, and thinking and reasoning capabilities.
Aside from BioVie’s NE3107, what are some of the latest treatments for Alzheimer’s and Parkinson’s?
In Alzheimer’s, the FDA granted accelerated approval earlier this year to a new treatment from Eisai and Biogen called lecanemab, sold under the brand name Leqembi, based on its ability to slow cognitive decline by 27%.
It’s the second approved for Alzheimer’s in a new category of medications called monoclonal antibodies. Leqembi is given via an IV and aims to reduce the number of plaques in the brains of Alzheimer’s patients.
Some of the Alzheimer’s treatments currently in drug trials include Cassava Sciences’ candidate simufilam. Rather than reducing the number of plaques, this treatment aims to stabilize a different protein called altered filamin A. Cassava believes that binding filamin A keeps ß-amyloid from forming in the brain, preventing the plaques believed to be to blame for Alzheimer’s symptoms.
In Parkinson’s, some of the new treatments undergoing trials include a drug called buntanetap from Annovis Bio. Buntanetap aims to target multiple proteins implicated in neurodegenerative disease by reducing inflammation.
Additionally, Anavex is developing blarcamesine, which prevents toxic mRNA from being translated into proteins, and Denali is developing DNL151 in partnership with Biogen. The drug candidate blocks the leucine-rich repeat kinase 2 (LRRK2) to restore lysosomal function and counter the pathogenesis of PD.
How does BioVie’s drug candidate differ from the others undergoing trials?
At this point, few of the new Parkinson’s and Alzheimer’s drugs undergoing clinical trials are aimed specifically at reducing inflammation. Like buntanetap, BioVie’s NE3107 aims to reduce inflammation in the brain and is being tested in both Alzheimer’s and Parkinson’s. However, our drug candidate does this in a different way.
NE3107 targets TNF-α, the master regulator of inflammation, to block the inflammatory cascade that results in a feedback loop that causes more inflammation in the brains of Alzheimer’s and Parkinson’s patients. On the other hand, Annovis Bio’s buntanetap targets proteins believed to be toxic to the brain, thereby reducing inflammation.
How can patients try to reduce their chances of developing Alzheimer’s or Parkinson’s?
As with all chronic medical conditions, the best things people can do to reduce their chances of developing Parkinson’s and Alzheimer’s include exercise, improving their diet, and being careful about the environment they expose themselves to.
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