Alzheimer’s disease has been particularly vexing for medical researchers for a number of reasons, including the fact that genome-wide studies have identified more than 40 genetic loci associated with the disease. But digital twin technology presents a promising way to break down the challenge into smaller components, eliminate some possibilities, and find the path to a cause on an individualized basis.

Dr. Cory Funk is focused on Alzheimer’s in his role as a Senior Research Scientist at the Institute for Systems Biology, a nonprofit biomedical research organization based in Seattle. In a talk at Upgrade 2021, Dr. Funk reported on his work with digital twins to “reduce the hypothesis space by means of causal reasoning.” It’s an important endeavor because there is so much variability in how the disease manifests itself, with the same inputs appearing to cause Alzheimer’s in some individuals but not others.

These variations contribute to what makes Alzheimer’s research so difficult, resulting in more than 400 failed clinical drug trials, at a cost of upwards of $200 million per trial, Dr. Funk said. On top of that, Alzheimer’s is expected to consume vast resources from Medicare and Medicaid in coming decades. “So there really is a huge economic burden with Alzheimer’s,” he said.

In terms of research, the problem stems from the lack of a causal framework that can help researchers understand what causes Alzheimer’s in any individual patient. “We can make generalizations about them, but for a single person, it’s really hard to understand mechanistically what’s going on,” Dr. Funk said.

The solution lies in creating functional processes that model pathways within the brain as sort of an intermediary step. Those pathways can be modeled with digital twin technology. At that point, researchers can then connect various genomic factors with the functional processes, and eliminate some confounding factors along the way. “You’re breaking down the problem,” he said.

“This is sort of the basis of how we could potentially personalize medicine, if we can bridge this gap and can understand those genomics and how they relate to those functional processes,” Dr. Funk said.

To date Alzheimer’s research is quite fragmented, with few if any organizations trying to integrate all known nuggets of causal reasoning into a full model. But that’s the idea behind the EmbodyBio Brain Health and Neurodegeneration model, a digital twin model for use by Alzheimer’s researchers, among others.

“EmbodyBio has created a model and they’ve broken it up into 13 different subsystems,” he said. “They based it on over 500 references, so really scouring papers for the biology and trying to capture that biology within their model.”

With such a model, researchers can now look at the risk factors that might contribute to Alzheimer’s over the 25 years or so during which the disease develops and progresses. “You’ve got to be able to model basically the entire lifetime of an individual if you want to understand Alzheimer’s,” Dr. Funk said.

To learn more about his research view the full video of his talk above, or click below for a transcript.

Presented at the NTT Research Upgrade 2021 Summit on September 21, 2021.

Click below for the full transcript.