When first infected with the Lyme disease-causing bacteria Borrelia burgdorferi, humans only have minute concentrations of the organism in their blood. Could the same technique used in an MRI help healthcare providers detect early stages of infection? For more than a decade, T2 Biosystems Inc. has worked to apply magnetic resonance technology to direct diagnostics, receiving the first and only Food and Drug Administration (FDA) clearance for a blood test that can identify sepsis-causing pathogens without a blood culture. Now, the team is one of 10 Phase 1 winners that have advanced to Phase 2 of the LymeX Diagnostics Prize, a prize competition to accelerate the development of Lyme disease diagnostics.
Through September 2023, the Phase 2 cohort is participating in a virtual accelerator designed to help them refine their concepts for detecting active Lyme disease infections in people. The goal of the multiphase LymeX Innovation Accelerator (LymeX) competition is to nurture the development of diagnostics toward FDA review.
We spoke with T2 Biosystems’ Director of Molecular Sciences Jessica Snyder to understand how the team is considering the unique barriers to an active Lyme disease diagnostic, patient usage, and potential for future applications of their research.
T2 Biosystems has helped lead research in applying magnetic resonance technology to direct tests for diseases that are difficult to detect, such as sepsis. How did you apply those learnings to Lyme disease?
Snyder: ”Several years ago, we started to work around Lyme disease and look at it as a possible disease for our technology to work with. When we heard about the LymeX competition, we were like, ‘Oh, this is great. This will give us some renewed vigor for working on this test and getting it to the point where we could go somewhere with it.’ We’re really hoping to be able to use these connections for figuring out the tricky regulatory pathways that we need to take to bring such a test to market. We’re lucky to be in a spot where we have people working at the company who have worked with Lyme disease before, and so we were able to get a really excited team together.
The unique part of our sepsis testing is that we’re able to do very, very sensitive detection directly in blood. The paradigm for other tests tends to be that you have to do a blood culture and grow those bacteria so they’re at a higher concentration, and then do molecular testing. But we’ve found some unique processes and chemistries that allow us to do detection directly in blood when there are only one or two cells there. We can get an answer very quickly, instead of having to wait for blood culture.
The concepts are really the same. We’re detecting really low concentrations of organisms. Instead of sepsis-causing bugs, it’s B. burgdorferi that causes Lyme disease. We’re looking at ways to make it as sensitive as possible for the particular B. burgdorferi organisms. They have some unique things going on with their genome.
We’re figuring out how to approach the genetic component of it, plus how to grow these organisms for research. Doing B. burgdorferi cell culture is not an easy thing. So we have to grow all these various species and get them into blood at really low—but precise—concentrations. We concentrate the sample so that we can find maybe one or two B. burgdorferi or Lyme disease-causing pathogens within that sample. Our system basically amplifies the DNA from that sample, and then we can detect it very sensitively with our magnetic resonance technology. So it’s a unique, sensitive way of determining early stage active disease.”
As you noted, the genome of Borrelia burgdorferi is particularly complex—one of the many barriers to developing a diagnostic for active infection. How does T2 Biosystems’ concept address these challenges?
Snyder: ”Our test is based off of the same techniques for an MRI. It’s a specific subset of magnetic resonance technology. We’re not doing imaging, we’re just doing what’s called the T2 relaxation testing. In our samples, we amplify the DNA and we add in these super paramagnetic particles. They’re basically iron oxide particles that have probes that bind to the DNA attached to the surface of the particles. So when we amplify the B. burgdorferi DNA, the particles then start to bind to that DNA and they become clusters of particles within the solution. The magnetic resonance then would measure that solution, and it’s actually measuring the water relaxation.
So if the DNA is present and you get the clustering, then you get a high T2 signal. If it’s all dispersed particles, then you get a low T2 signal. We have a small, toaster-sized magnetic resonance reader within our devices that the sample tube goes in, and then you get these outputs. You can easily tell the difference between the DNA being there or not there. And one of the unique parts of this is it works in really messy samples. Unlike an optical measurement, it doesn’t care if it’s a complex, bloody sample.”
If a Lyme disease test is reviewed and cleared by the FDA, the next step would be to make it widely available to the public. How do you envision patients would be able to use and benefit from your test?
Snyder: ”The more that we learn about the life cycle of B. burgdorferi during infection, I think there’s definitely a need for early-stage testing that the serology is just not set up well to do. If it’s early disease, it makes a lot of sense to use an early active blood-based test like ours. Based on literature, the B. burgdorferi organism seems to disseminate to other places within the body over time, and then potentially it’s not heavily concentrated in the blood at later stages. An early Lyme test could be compatible with current FDA cleared serology testing that is more effective at a later stage or if there is some uncertainty on the timeline of the disease.
Currently for sepsis testing, our device itself does all the processing. It’s a fully automated bench-top device that does all the blood processing, but also has that little toaster-sized magnetic resonance reader in it that can do the readings. We’ve typically put that device into larger hospitals. We have customers throughout the United States and in Europe, and then select other sites in the world. We’ve already set up that paradigm for sepsis testing, which makes sense because the samples are sent to a central lab or similar for the testing purposes.
For Lyme disease, though, there is a question about what is the best way to get to the people who need testing. When you think about Lyme disease testing, it’s not someone that’s in the emergency room, it’s someone who’s going into their primary care physician. Those samples would be collected and potentially sent somewhere. We also have good geographic distribution with our current instrument install base, so we are looking at different options to help clinicians detect active early Lyme disease.”
Besides the LymeX Diagnostics Prize’s monetary awards, the 10 teams in the Phase 2 virtual accelerator have access to a range of resources over the course of nine months. Given T2 Biosystems has been working on Lyme disease diagnostics for several years before the competition, what has been most helpful?
Snyder: ”We’ve already had a great one-on-one with Liz Horn. We were able to get in for her office hours, and we had a lot of questions regarding samples and clinical studies. She was a fantastic expert who gave us so much information, and that was a really phenomenal aspect—just being able to get some of those questions answered in a direct manner. The webinars have been good, too.
There’s a lot of information that we’re getting. It’s nice to have the help with some of these questions because we’ve been working on Lyme disease for quite some time. We’ve had our own difficulties with trying to figure out some of these questions, and having the support of experts has made us very excited about this accelerator.”
What are the next steps for T2 Biosystems’ Lyme disease test and your work in applying magnetic resonance technology to direct diagnostics?
Snyder: ”We’re actively talking right now about what it would take to commercialize the Lyme disease test. We’re also talking a lot about how to set up our clinical trial, because we have this momentum right now. Besides that, our company has other tests going on in the sepsis realm. We’re also currently working on resistance gene testing, which is still in the sepsis area, such as for carbapenemases and methicillin resistance.
Lyme disease is definitely a departure from what we’ve done in the past. I think we all understand the implications for sepsis and early detection, and how that could change the current medical paradigm and the amount of lives that it could save.
With Lyme disease, you’re able to potentially have a strong impact on the health and well-being of people in a large area with rapid testing. Just to have people think that, ‘Oh, yeah, I’m going to go and get my rapid testing.’ It’s something that could be a normal thing that happens. I think that could have such an impact on patients’ lives.”
Looking ahead: Expert judging panel to convene in October 2023
Following the accelerator, the cohort will submit concept papers that detail solution refinement, clinical and patient input, and a roadmap from lab to market. The competition judging panel—composed of experts across biology, clinical and technology translation, patient experience and advocacy, diagnostic science and technology, exponential innovation, and ethics—will evaluate eligible submissions according to official Phase 2 evaluation criteria. Based on the judges’ evaluations, the panel will recommend up to five Phase 2 winners of the LymeX Diagnostics Prize.
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