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Will We Ever Find a Cure for Dementia?

AARP's $60 million investment supports research into promising treatments


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Brad Margus is hoping to discover answers to some of medicine’s biggest mysteries by peering deep inside the brain.

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Locating the specific gene that’s responsible for igniting inflammation near the brain’s memory center could lead to a targeted treatment that minimizes brain injury in people with Alzheimer’s disease. And knowing which cell-specific proteins are responsible for producing motor symptoms of Parkinson’s disease may bring about a drug that disables them.

This precise approach “makes it possible to make drugs that only act on the cell type you care about,” reducing the unwanted side effects that most drugs have, says Margus, chief executive officer of Cerevance, a Boston-based drug development company focused on brain diseases. What’s more, it could lead to a major breakthrough in the field of dementia research. About 50 million people worldwide suffer from dementia, and still there is no treatment to stop or slow its progression.

Investing in cutting-edge research

Cerevance is among several companies pursuing new cutting-edge dementia treatments that received recent financial support from the Dementia Discovery Fund (DDF), a $350 million London-based venture capital group that invests in promising new therapeutic projects. In 2018, AARP committed to invest $60 million with DDF to support the quest for a dementia cure.

“AARP’s investment is one example of how we are working to improve the lives of older Americans,” says Scott Frisch, executive vice president and chief operating officer of AARP. “Millions of individuals and their families are affected by dementia, and the need for effective treatments has never been more critical.”

Others on the receiving end of DDF funding this year include QurAlis, a company working on treatments that target faulty cellular mechanisms in amyotrophic lateral sclerosis (ALS) and genetically related frontotemporal dementia (FTD), as well as Nitrome Biosciences, which is developing drugs against a newly identified class of enzymes that could slow or halt the progression of Parkinson’s disease.

“We’re finding that a number of biopharma companies are interested in chipping away at Alzheimer’s by learning more through ALS, FTD, Huntington’s and Parkinson’s,” explains Angus Grant, chief executive officer at DDF. Alzheimer’s disease is the most common cause of dementia.

This approach has worked before; Grant compares it to cancer’s treatment journey. Similar to dementia, “we realized cancer wasn’t one thing,” and required more than one treatment approach, he says. Studying the cell structure and genetics of the more than 100 different types of cancers eventually led to the development of a variety of treatments that, when used alone or in combination with one another, are more effective than a one-size-fits-all prescription.

With dementia, it may be that different forms of the disease share a common pathway to cognitive decline, and that a drug developed to treat Parkinson’s dementia, for example, can also help someone with Alzheimer’s dementia. “And we begin to see this more and more, where the aging brain defect is not specific for one disease, but it is specific for a molecular pathway which has been disrupted,” Grant says.

The DDF’s interest in homing in on treatments for specific dementia populations “where we have a better understanding” of the patients and the disease causing the dementia also increases the odds of finding a treatment that provides a more immediate benefit to patients and their caregivers, Grant explains. Since its 2015 launch, DDF has invested in 19 companies pursuing age-related dementia projects; several are in clinical trials.

Diversifying the drug pipeline

Scientists all over the world are following a similar path. They’re looking beyond the single strategy most dementia researchers have studied in the past — clearing toxic amyloid plaques from the brain, a hallmark of Alzheimer’s disease — and instead are pumping more possibilities than ever before into dementia’s drug pipeline.

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The roles the immune system and the metabolic system play in the development of dementia are under the microscope. Researchers — including many funded by the National Institutes of Health (NIH), which is expected to spend $2.8 billion on Alzheimer’s research in 2020 — are also studying everything from blood vessels to hormonal factors to solve the dementia dilemma.

“We now know that the brain is part of a larger system,” explains Rebecca Edelmayer, director of scientific engagement at the Alzheimer’s Association. “And there may be many other ways to target the overall health of the brain” so that it stays as fit as possible throughout the aging process and is able to “stave off signs and symptoms of Alzheimer’s disease and other dementias,” she adds.

“AARP’s investment is one example of how we are working to improve the lives of older Americans. Millions of individuals and their families are affected by dementia, and the need for effective treatments has never been more critical.”

—Scott Frisch, executive vice president and chief operating officer of AARP

Some of the most promising drug candidates in the packed pipeline of possibilities help to preserve and strengthen the communication channels between nerve cells, explains Suzana Petanceska, a program director in the Division of Neuroscience at the NIH’s National Institute on Aging, which is currently supporting more than 230 dementia-focused clinical trials – including more than 40 drug trials – and recently established two new research centers dedicated to diversifying the Alzheimer’s disease drug development pipeline. 

With dementia, these channels become damaged or disrupted, leading to memory loss and a cascade of debilitating effects. One theory currently being tested in clinical trials is that if we prevent the death of these neurons, or find a way to stimulate the birth of new ones, then the brain becomes more resilient when faced with disease.

“We all have resilience, but when we talk about how we protect the brain, some of the ways to do that is actually to harness the brain’s natural repair mechanisms and activate them so that it can recover in the face of injury,” Petanceska says.

The tricky part is figuring out the best time to target these processes. The symptoms of Alzheimer’s and other dementias typically set in later in life, but “the disease process begins many, many years before,” Petanceska explains. So having a “reliable, noninvasive” way to track warning signs of the disease before the damage is done will be key to delivering effective treatments.

The DDF’s portfolio also includes companies and projects that are investigating ways to protect the health of brain cells to treat Alzheimer’s disease and other neurodegenerative disorders. AstronauTx, for example, which received DDF funding in 2019, is focused on developing drugs to modify malfunctioning astrocytes, a type of brain cell that supports the neurons and their communication channels.

Advancements in amyloid and tau

All that’s not to say the treatment theories that held so much promise in the ’90s and early 2000s have been totally abandoned, despite decades of failed clinical trials. Much of the research in the field continues to focus on amyloid, as well as tau — another hallmark protein of Alzheimer’s disease that forms tangles inside the neurons.

This year, all eyes are on aducanumab, an anti-amyloid drug that is headed to the Food and Drug Administration (FDA) for review. It was shown in clinical trials to reduce the amount of amyloid in the brains of people with early Alzheimer’s disease. U.S. drugmaker Biogen reports that participants who received high doses of the antibody saw improvements in memory and thinking skills, and were better able to perform activities of daily living, such as laundry and personal finances. If approved, aducanumab will be the first drug available to treat people with Alzheimer’s disease. Currently, the handful of dementia drugs available help only to alleviate symptoms.

Christopher H. van Dyck, M.D., professor of psychiatry, neurology and neuroscience and director of the Alzheimer’s Disease Research Unit at the Yale School of Medicine, points to two other amyloid-clearing therapies that are far along in the clinical trial process — BAN2401 (from companies Biogen and Eisai) and gantenerumab (from Roche). If aducanumab doesn’t clear FDA review, “you’d bet on one of these” becoming the first available treatment for Alzheimer’s disease, he says.

Timing is one thing that sets the more successful and the promising anti-amyloid therapies apart from their failed predecessors. Until recently, every trial that aimed to stop or slow the progression of dementia failed. “And it failed because we were giving these drugs to people who have symptoms” of the disease, explains Michael Rafii, M.D., an associate professor of clinical neurology at the Keck School of Medicine of the University of Southern California, and medical director of the Alzheimer’s Therapeutic Research Institute.

Facts and Figures

Alzheimer’s disease is the most common cause of dementia. Other common causes include vascular dementia, Lewy body dementia, and neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease.

  • 50 million: Number of people worldwide with dementia.
  • 5.8 million: Americans age 65 and older living with Alzheimer’s disease; almost two-thirds of them are women.
  • 14 million: Number of Americans projected to have Alzheimer’s disease by 2050.
  • $305 billion: Cost in U.S. of Alzheimer’s and other dementias in 2020.
  • $1.1 trillion: Without a treatment, projected cost in U.S. in 2050. 

Source: Alzheimer’s Association

And giving drugs to people who are symptomatic “is just too late,” he says. Somebody who has dementia already has widespread damage to the brain. “And unfortunately, when there’s any damage to the brain, it’s permanent. You can’t go back. So early treatment is the key,” he adds.

To Rafii’s point, trials targeting people in the earlier stages of their disease have seen success. One new trial is even testing to see whether removing amyloid in people who have no Alzheimer’s symptoms will provide a preventative benefit. “So that’s a very exciting study,” Rafii adds.

Targeting the tau tangles is another big area of focus in the field. Unlike amyloid plaques, which can be present in the brains of people who are asymptomatic, tau tangles are more closely correlated with clinical symptoms of the disease. Plus, their presence is seen in a number of neurodegenerative disorders, not just Alzheimer’s.

“If we are able to find a therapeutic that is helpful for really staving off the changes that occur with tau, we may actually be able to find therapeutics that are beneficial to multiple dementias,” the Alzheimer’s Association’s Edelmayer says.

'Cure' could take many forms

As varied as the research pipeline is, most experts agree on one thing: When it comes to finding a way to stop, slow or prevent dementia, it won’t boil down to one drug treatment or even one drug target. Rather, it will be a combination approach, perhaps involving drugs that clear the amyloid plaques, knock out the tau tangles, target problem proteins and improve the synaptic health of the nerve cells in the brain.

Patients may also receive nonpharmacological prescriptions from their doctors. Some of the most recent research has shown that cardiovascular health and cerebral vascular health play a critical role in overall brain health throughout one’s lifetime. Exercise, diet and sleep have all been shown to reduce risk of cognitive decline in adults. What’s more, a landmark study in 2018 showed that intensive blood pressure control significantly lowered the chances that participants developed mild cognitive impairment.

The mishmash of therapies likely won’t cure dementia, but as Rafii explains, “we have very few cures in medicine.” He and others in the field, including the DDF’s Grant, are optimistic, however, that the ongoing advancements will lead to treatments that can delay the disease and improve the lives of millions.

“What I’m seeing is great progress in the building blocks, the foundation of new future therapeutic approaches,” Grant says.

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