Dr. Mark Eshoo and Heather Carolan have studied Lyme disease for over a decade, leading research at Abbott and Ibis Biosciences, Inc. for direct Lyme disease molecular tests. Driven by an interest in novel biosensing technology for next-generation, low-cost diagnostics, Eshoo founded BlueArc Biosciences Inc. in 2018. 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 Food and Drug Administration (FDA) review.
We spoke with BlueArc Biosciences Founder and CTO Dr. Mark Eshoo, Director of Bioinformatics and Data Science Heather Carolan, and Assistant Research Scientist Chase Varga to understand how the team is applying their prior research to the LymeX Diagnostics Prize, considering diagnostic accessibility to clinicians, and looking ahead to next steps for their test.
The BlueArc Biosciences team has comprehensive experience in developing Lyme disease diagnostics. How is your team using prior research to inform your approach to the LymeX Diagnostics Prize?
Eshoo: “Heather and I have been working together on Lyme disease and tick-borne disease-related problems together since about 2007. She’s been my go-to person when it comes to working on this problem. Chase is a college student and an intern, and he’s getting experience now in developing Lyme diagnostics and learning about the challenges.”
Carolan: “I have post-Lyme disease syndrome, so that was one thing that made me want to find a diagnostic for Lyme disease. In 2007, I hunted down Ibis Biosciences to work there and to start on tick-borne disease, and was there for about 10 years. Mark and I have recently reconnected, and now I’m helping with assay design. I’m really passionate about trying to get a reliable diagnostic for early Lyme disease out there.”
Eshoo: “Our focus has been on diagnostics, but we’ve published over a dozen papers on tick-borne diseases and Lyme disease together. We’re trying to answer questions too. When we were with Abbott Labs, we tested thousands of ticks from all over the world; we’ve looked at blood samples with people clinically diagnosed with Lyme disease and at serial blood samples from people with Lyme disease during and after their treatment.
Though we’ve been developing a diagnostic, we’ve been really at the forefront of using diagnostics to answer important questions, like how long does Borrelia burgdorferi [the bacteria most commonly responsible for Lyme disease] stay in the blood? How well does it respond to treatment? There are actually different strains of B. burgdorferi, and we could tell them apart with our tests we ran in the past. How does that impact what you see in the environment and what you see in the patients?
Currently, the diagnostic tests that are out there today are looking for the human immune response to that infection. That immune response can often take up to a month to fully develop. We’ve seen in some of our previous studies that some patients never developed that immune response, so they test negative even though they’ve clearly had Lyme disease.
Rather than looking at the immune response—also sometimes called seroconversion—we’re looking directly for the bacteria, the causative agent of the infection. It is clearly there at the very beginning, because that’s why the people are getting symptoms and sick. By directly detecting the B. burgdorferi, we’re going to be able to diagnose it earlier, especially in patients who are at that first doctor’s visit saying, ‘Hey, I don’t feel well, what might this be?’”
BlueArc Biosciences’ test identifies unique B. burgdorferi molecular biomarkers in blood. Tell us about how you’re approaching a diagnostic for active infection.
Eshoo: “One of the big challenges is, how do you know how sensitive your test is when you have nothing to compare against? When we compare against serology for early Lyme disease, serology is about 25 to 30% sensitive. So what is our gold standard reference test? There is no gold standard today. That’s really been one of our challenges. We did a study where we compared punch biopsies from skin and blood. Skin punch biopsies were actually a very good reference because they have the highest levels of B. burgdorferi. It’s obviously not a suitable sample for a diagnostic test, but for a reference test, PCR from a skin biopsy was quite good.
There’s very little B. burgdorferi in the blood, but it is in the blood. We have to remind ourselves that a tick is not very big and when they feed on blood, they feed on a poppy seed worth of blood. But they transmit infection very efficiently, so it is there in the blood. The trick is having enough samples and very efficient processes: You’re only as good as the efficiency of your process. Every step of the way is very important.
So in the amount of blood you start with, how do you concentrate the B. burgdorferi bacteria from that blood? That’s very important. And most people wind up losing 80% of the B. burgdorferi that’s in that blood during that sample processing. Every step of the way, you don’t gain sensitivity, you lose it. So being very efficient and mindful of each of those steps is very important.
We start with a moderate volume of blood, nothing outrageous, and we’ve developed protocols that are exquisitely efficient and which we’ve validated. Some of these came from my experience working on forensics of trace DNA samples. But learning how to not lose a few molecules of material is very important. Every component that you use in that process becomes very critical. We’re really building on a lot of know-how and previous experience to not lose any material in the process. We’re also looking at biomarkers that are relatively abundant, so even a few bacteria give us a strong signal.”
Treatment is most effective in the early stage of Lyme disease—but access to diagnostics is obviously critical to receiving care. How is the team incorporating clinician and patient needs into test design?
Eshoo: “Importantly, our tests are designed to be run on equipment that’s already in diagnostic labs today for COVID-19 testing. So there’s no equipment that a testing lab would need to buy in order to run our test. It will run on existing technologies. If you have to buy a $400,000 instrument and have a full-time person running it, that’s a barrier to entry. We want to make sure that our test is available to all clinicians and their patients.”
The LymeX Diagnostics Prize is helping teams develop tests for active infection through a range of monetary and non-monetary resources offered as part of the Phase 2 virtual accelerator. What has been most beneficial to your team?
Eshoo: “I like it all—the webinars that we’ve had have been top-notch. Even from people I know who gave some of those webinars, I learned a lot from their presentations that I didn’t know. So that was quite beneficial. And of course, research is not a cheap venture, and having access to the funding has been very important for us too. If anything, that’s the game changer.”
Varga: “Going into this field, it’s great to see the passion of the Lyme disease community and all the knowledge that everyone here has put together. So it’s been such a learning experience, gaining from this knowledge and trying to give back.”
Through September, BlueArc Biosciences will be working with the accelerator’s advisors and subject matter experts to refine its test. What comes next for your team?
Eshoo: “We hope to carry this to the next level. So our goal is to demonstrate the performance of the test. Beyond that would be then getting into—potentially—clinical studies and working with the target users, which for us would be clinical diagnostic labs and getting their input to make sure that we’re in sync with their needs and workflows.
Our approach is quite novel, and so it could have implications for other diseases, particularly bloodborne diseases. Things like sepsis certainly come to mind, and other pathogens of that nature. We may be getting ahead of ourselves, but Lyme disease is one of the toughest problems there is, and that’s why we’re having this conversation today. And so if we can succeed at Lyme disease, there’s a lot we could do.”
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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