Disrupt Dementia Banner with the text: Sparking bold new solutions for the world’s brain health crisis doctor looking at brain scans Brad Margus is hoping to discover answers to some of medicine’s biggest mysteries by peering deep inside the brain.
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.
The roles the immune system and the metabolic system play in the development of dementia are under the microscope. Researchers 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.
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 National Institute on Aging.
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 […]