Esya Labs Leads Paradigm Shift in Alzheimer’s Using Novel Biomarkers and AI for Revolutionary 360° Perspective of Disease
In her lab at the University of Chicago, Chemistry Professor Yamuna Krishnan creates meaningful chemistry-driven approaches that enable the analyses of biological samples in new ways.
One of these technologies is a chemical imaging platform capable of measuring ion levels inside the lysosomes of live patient cells. This provides unprecedented insight into the metabolic status of a cell and allows researchers to tell apart healthy cells from diseased ones.
The platform uses synthetic DNA strands that have been engineered to function in a specific way. These so-called “DNA nanodevices” are used to measure lysosomes’ performance by creating chemical maps of their activity – a process that had previously not been possible.
“We spun this research out into a company, Esya, to tackle a huge problem: early detection of neurodegenerative diseases and pre-selecting the right treatment for the patient in a personalized manner,” said Krishnan, who is the company’s cofounder and chief scientific officer.
“So, at Esya, we licensed this pioneering ion mapping technology that reports the unique chemical composition of each lysosome with the vision of addressing this problem, by building non-invasive, rapid precision diagnostics and to facilitate personalized medicine,” explained Dhivya Venkat, Esya cofounder and CEO.
Combining these novel techniques with a proprietary artificial intelligence (AI) based platform uniquely positions the company to detect any lysosomal dysfunction early, and in turn, diagnose associated diseases.
Among these is Alzheimer’s disease (AD), which is notoriously difficult to treat for several reasons. However, recent research suggests AD is caused in part by lysosomal dysfunction. “We are at the forefront of a paradigm shift in how Alzheimer’s is approached,” said Dhivya, “new research supports the hypothesis that Aβ and tau in AD are the consequence of defective autophagy and lysosomal dysfunction.”
The Paradigm Shift
Esya is the first to propose a non-invasive diagnostic using their insight into lysosomes as a biomarker for AD – marking a significant change from the currently available methods.
The company has eight different DNA nanosensors that provide a multi-pronged way of looking at lysosomes, allowing them to create an effective model to accurately diagnose AD patients. “Additionally, our novel biomarkers can help accelerate drug development by monitoring the effect of pharmacological interventions on a selected population of lysosomes,” explained Dhivya. “We can also test the efficacy of currently available Alzheimer’s drugs to recommend the most effective drug for an AD patient, facilitating the development of personalized medicine.”
Krishnan and Dhivya said this approach will provide a “revolutionary 360° perspective” of AD. This includes a precise standalone diagnostic, precision medicine for personalized treatments, and the ability to monitor and measure disease progression.
“We have also made great strides on our precision medicine proposition, evaluating the impact of various drugs on the biomarker signatures,” added Dhivya, noting that they can possibly detect the disease even earlier than anticipated.
“We recently showed that the ion signatures from lysosomes from patient-derived cells respond, changing in the right direction when treated with the right drug, and remain unchanged when treated with the wrong drug,” explained Krishnan. “This was very exciting for us because right now, patients with Alzheimer’s disease are randomly prescribed any one out of the five approved drugs, and it’s chance whether you get the right one for you from the get-go. Meanwhile, if you are unlucky and it hasn’t worked well, not only have you lost time, your condition has probably worsened.”
The AI Platform
Esya’s core value proposition is reinforced by its proprietary machine learning platform, which it is building in-house. To create a unique set of AD-relevant data, the company is supplementing its subcellular data with proteomics, metabolomics, genetics, and clinical data.
“Machine learning-driven algorithms using our multi-omic dataset will allow us to identify and stratify AD,” explained Venkat, “allowing us to get to a 360 perspective across diagnosis, treatment and disease progression.”
Thinking ahead to the automation and scalability of its products and research, the team also has developed its Esya Proprietary Algorithms into an analytics program for biomarker discovery.
“We are analyzing a large-scale and well-characterized dataset of AD patients alongside healthy, aged individuals’ lysosomes in our UK lab facilities,” said Dhivya. This will allow the company to build its diagnostic algorithm and establish the diagnostic accuracy of its candidate biomarkers.
The company is currently working on two drug discovery partnerships with two of the world’s top five pharma companies, including Novartis. Still, a significant part of the focus will remain on research “to ensure that we maintain our edge at the forefront of this paradigm shift in neurodegenerative diseases,” said Venkat.
As Esya grows, Souvik Modi, the co-inventor of Krishnan’s prototype sensors and patents has recently joined the team to lead the UK lab, which was opened to mitigate challenges related to COVID and subsequent US visa restrictions.
Last year, Esya raised more than $1 million in its seed round, which has catapulted its research efforts forward. Current research projects underway should see the company release a pilot diagnostic next year. “This would bring us to an inflection point that we are already starting to prepare for – a lack of sufficient biobank available AD samples means we need to scale the company quickly to conduct clinical trial programs,” explained Venkat, noting that the goal is to have a product market-ready in the next two years.
“I expect we will be able to deliver an AD diagnostic and help select the right drug for every new AD patient from the get-go, and successfully slow the progress of AD as a result,” added Krishnan. “It should not be a matter of luck that you receive the right drug when you are diagnosed with AD.”