Willy Wonka, Inflamed Brains and Overactive Immune Systems: How JLABS Companies Are Exploring the Forefront of Alzheimer’s Research

Articles

It’s been more than a century since German psychiatrist Alois Alzheimer first diagnosed a patient with the disease now associated with his name, and yet we’re still discovering new facets of the condition.

Many theories exist as to why people develop Alzheimer’s and potential ways to treat it. Janssen is studying a variety of approaches to slow disease progression or prevent the disease from leading to dementia and also to potentially recover brain function. And we’re not alone: there are currently 500 active clinical trials focusing on Alzheimer’s, according to ClinicalTrials.gov.

This week, for World Alzheimer’s Awareness Day, we’re publishing several different pieces of content to explore what the current science tells us about the disease; some exciting prospects for future research; and profiles of companies working on the cutting edge of the space.

This latter category is the focus of this blog. JLABS has 20 current residents working in the field of neuroscience, many of which have insights that could enlighten our understanding of Alzheimer’s disease. We interviewed some of these companies to better describe their work.

WinterLight Labs

Alzheimer's disease, the most common cause of dementia, impacts 5 million Americans, a number that is expected to triple by 2050. Yet we now know that memory loss is only the end stage of what begins a decade or more earlier. What if we could identify early signs of the disease, years before they become apparent? WinterLight Labs has developed a system they say could do just that.

The company, based in JLABS in Toronto, has a novel technology that uses artificial intelligence to analyze speech and language patterns to help detect and monitor cognitive and mental diseases. The current most commonly used tool to accomplish this is the Mini Mental State Exam, or MMSE, an in-person interview that can be time consuming and difficult to administer, as well as somewhat subjective, says Liam Kaufman, CEO of WinterLight.

WinterLight’s software listens to a person’s vocabulary, syntax, grammar, pitch, tone and hundreds of other variables as they describe a picture. It can then make a cognitive assessment, with 82 percent accuracy or higher, from a few minutes of speech recordings. This can help identify early signs of Alzheimer’s, as well as other cognitive declines, Kaufman said.

“Our hypothesis is that once we get more information from each person, we will have their own history as a baseline,” Kaufman said. “In nursing homes, for instance, this could be used understand how far along someone with Alzheimer’s is, and track their cognitive changes over time.”

The program is partly based off research Kaufman’s colleagues conducted by studying decades of interviews of the actor Gene Wilder, who died in 2016 at the age of 83 from complications of Alzheimer’s disease. Wilder began his acting career in the 1960s and is well known for his portrayal of Willy Wonka in the 1971 movie, Willy Wonka & the Chocolate Factory.

Because of Wilder’s lengthy career in the public spotlight, WinterLight was able to analyze Wilder’s interviews from different decades to look for early signs of the disease. Kaufman said the software was able to pick up inflection points from the interviews that in retrospect, indicated a cognitive change associated with Alzheimer’s.

With their technology, WinterLight hopes to provide the same insights for a much broader population.

Cortexyme

The physical hallmark of Alzheimer’s disease – the “peculiar substance,” that Alois Alzheimer first described as accumulating in the brain of a patient early in the 20th century – are amyloid plaques, or what we now know are collections of protein pieces called beta-amyloid.

For decades, it was widely accepted in the scientific community that these plaques kill healthy brain cells, and that their build-up in the brain is what lead to the cognitive decline in Alzheimer’s patients. One new theory of Alzheimer’s is that the plaques themselves aren’t what’s causing the disease, but simply an after-effect of a much better understood condition: infection.

What if the plaques are actually the result of the body trying to protect itself from invading viruses, bacteria or fungi? As we age, pathogens can gain access through a variety of mechanisms including a leaky blood brain barrier As a response, the brain creates the beta-amyloid plaques to trap the microbes, like an insect in amber.

This interesting idea is what’s driving Cortexyme, a South San Francisco JLABS company. “By developing a therapy that can rid the brain of a microbes we can stop Alzheimer’s in its tracks,” said Casey Lynch, CEO of Cortexyme.
 
“When we clear the bacteria at its source, all of the downstream pathology including neurodegeneration, amyloid production, tau fragmentation, and inflammation resolve,” Lynch said.
 
The company has completed proof-of-concept studies in multiple animal models and is currently conducting investigational new drug-enabling studies.

Tiaki Therapeutics

Another intriguing potential culprit in Alzheimer’s are microglia – immune cells that normally clear infections in the brain. Microglia can be found eating away at beta-amyloid, but their exact role is still an area of inquiry: are they keeping the spread of Alzheimer’s at bay, or do they play some causative role? Because microglia marshal an immune system response, they can sometimes overreact, causing chronic inflammation. This state of imbalance is associated with neurodegenerative disease, which contribute to neuronal dysfunction and dementia.

However, microglia are very difficult cells to study in the lab or in animal models, because they do not fully replicate the human condition. New models are needed to authentically study microglial biology. Tiaki Therapeutics, based at JLABS @ LabCentral in Cambridge, MA, aims to remedy this problem with its platform technology, which enables discovery and validation of targets that restore normal, homeostatic functions of microglia in the central nervous system.

“There are some key gaps in our ability to target microglia with therapies,” said Barbara Tate, acting CEO of Tiaki. “So Tiaki is set up to fill those gaps. It’s also complementary to other approaches, including those that target beta-amyloid.”

Tiaki was created and is funded by the Dementia Discovery Fund, an innovative venture fund that allows charity, industry and the government to provide investment in innovative dementia research.


These are just some of many JLABS companies working on cutting edge approaches to Alzheimer’s and other areas of need. If you’re interested in learning more about our companies, or applying for a residency, please check out our website.