Mimi:
Welcome to the Lyme 360 Podcast for all things related to Lyme disease and other chronic illnesses. I'm Mimi MacLean, mom of five founder, of Lyme 360 and a fellow Lyme warrior. Tune in each week to hear from doctors, health practitioners and experts to learn about their treatments, struggles and triumphs, to help you on your healing journey. I'm here to heal with you.

Mimi:
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Mimi:
Welcome back to the Lyme Podcast. This is Mimi MacLean, and today's guest is Dr. Regina Lamendella, she goes by Gina. And she is responsible for developing and leading the next generation sequencing diagnostics for infectious diseases for Contamination Source Identification, which is called CSI. And they are a new company that are trying to come up with the perfect diagnostic tool for Lyme disease in addition to other modalities as well.

Mimi:
Great thing about Gina is she is also a fellow Lafayette alumni, which I just found out about. I'm excited to have her on so she can talk out all the things that CSI is doing and how it is going to help the Lyme community. To get my detox for Lyme checklist, go to Lyme360.com/detoxchecklist.

Mimi:
Gina, thank you so much for your time today. I am excited to hear about CSI. I heard about you guys, I think from Carrie Perry, and she had been exposed to you and what you guys are up to and you're cutting edge. So I'm excited to dive in and share with other Lyme warriors about what you guys are up to and your clinical trials, and hopefully, potentially some really cutting edge stuff as far as diagnostics for the Lyme community. So thank you so much for coming on.

Dr. Regina Lamendella:
Thanks for having me, Mimi.

Mimi:
Yeah. So let's start out by explaining what CSI is, your company, and then we can go on to how you got involved.

Dr. Regina Lamendella:
Absolutely. So CSI stands for Contamination Source Identification. We are a CLIA-certified laboratory. We leverage very cutting edge molecular tests to diagnose the source of infections. And we have three primary infectious disease states that we're working towards clinical validation on. That includes Lyme disease and other tickborne diseases, prosthetic joint infections, as well as sepsis. These are three critical disease states where the currently available diagnostic tests are substandard like PCR, culture, antibody tests. They suffer from a lot of issues associated with specificity, sensitivity and timeliness to results. So our hope is to really change the gold standard for infectious disease diagnostics and to get physicians the answers they need.

Mimi:
How did you get involved in the company?

Dr. Regina Lamendella:
Yeah. So myself and two co-owners, Justin Wright and Gary Shope. Justin was one of my first research students at Juniata College, I'm a professor there in bioinformatics and molecular biology. So we actually started a different company looking at the microbiome. So I've studied the role of the microbiome and the etiology of lots of different disease states for a couple decades now. And we started a research based company, and then we met another Juniata alum, Gary Shope, who has extensive business experience. And we all came together in 2018. I think Gary, with his medical expertise and business expertise, he saw an opportunity to leverage this microbiome and these molecular techniques to help revolutionize diagnostics.

Mimi:
That's great. Now what makes CSI different? There are, as you know, many Lyme tests out there. A lot of them are not reliable or they're not as accurate as we'd like, they give you false positives, false negatives, expensive. Why is yours going to be different?

Dr. Regina Lamendella:
Yeah. So this diagnostic test, I liken it to fishing with dynamite. The currently available tests generally only look at one or two organisms, especially in guard to Lyme disease, a lot of those tests look at just Borrelia species. This test system, like I say, is fishing with dynamite in that we can look at thousands of pathogens, whether they're viruses, bacteria, fungi, other eukaryotic pathogens. This test system looks at the total RNA signature of the microbes in a sample. And that's really powerful because a lot of the tests, like I was mentioning suffer from sensitivity and specificity, and they're only fishing with hooks, right? They're looking for maybe one or two or a handful of pathogens when we know there are hundreds of pathogens that cause many different disease states. So we really think this comprehensive RNA based test is looking at not only everything there, but who is active.

Dr. Regina Lamendella:
And that's what a lot of the currently available test systems suffer from, a lot of the DNA based and PCR based test systems that are currently available, target DNA. And DNA has a really long half-life. You can go swab a dinosaur bone and get DNA from it. And because of that long half-life, we don't know whether that organism's alive or not. Whereas with RNA, there's a really short half-life. When that cell has li or died, the RNA only hangs around for about 30 seconds or so. So that RNA is a really good thumbprint for the active organisms causing a given infection.

Mimi:
Now they always say Lyme or the co-factors like to hide. They'll go in the brain and go in the blood brain barrier up there. And so when you do test, sometimes they're not active in the blood. Does your testing, is that affected by that, if they're hiding or in a dormant stage?

Dr. Regina Lamendella:
Yeah, absolutely. So one of our test systems that we're currently validating is a urine based system. And so we have the individuals interested in using our test, to do what's called a lymphatic flush. They essentially walk around to get things circulating through the system, and then everything gets shed into the urine specimen. And so we believe by targeting the urine as well as the blood, that gives us a better chance at detecting the etiological agent that might be causing Lyme or other tickborne diseases. Because we know, when you get bit by a tick and that pathogen or pathogens get into your system, they're at a really low titer, concentration, somewhere in the range of maybe 50 cells per milliliter. And they don't hang around in the blood. Borrelia doesn't hang around in the blood for very long. It goes on and hides out, like you said, in all different places in the body. And so we think it's really critical to evaluate not only blood-based tests, but urine based test to try to capture that evasive pathogen.

Mimi:
So you do both. And when you do a test, you ask for blood and urine.

Dr. Regina Lamendella:
Yes. We're doing a dual approach where we're validating on both blood specimens, as well as urine specimens, to give us a dual prong approach and a best shot of detecting that pathogen or pathogens.

Mimi:
Where are you at, in the clinical trial? Are you doing clinical trial to prove that it works, or you doing clinical trial so you can get insurance write offs? What's the purpose of the clinical trial?

Dr. Regina Lamendella:
Yeah, that's a great question, Mimi. And so again, I think it's both. So we know our analytical validation work went swimmingly well. We know that we can detect down to a couple cells, three or less cells per milliliter in urine, which is an unparalleled level of detection in terms of sensitivity. And in terms of specificity, we're looking at somewhere in the 99.99% specificity range. In other words, we can identify with nearly 100% accuracy, the species of the organism causing the infection. And so once you do analytical validation, which we've completed, you have to move to what's called clinical validation. That way this can become a clinically available diagnostic test that physicians can order. We're also considering direct to consumer testing as well, to try to get this test out to as many individuals that are suffering as possible. And then absolutely, yeah, once we get these studies published, then we can go for what's called a CPT code and insurance reimbursement code. So that's sort of where we're headed.

Mimi:
And how long does that typically take, that whole process?

Dr. Regina Lamendella:
That entire process, so analytical validation took us about six months. And like I said, that went really well. And now clinical validation I'm thinking is going to take us one more Lyme season. We're really looking for interested parties to become part of our IRB approved study, to submit samples because we need that clinical data again, to become a clinically valid, CLIA-certified test. I think that's going to take another, probably six to nine months. And then the CPT code process is pretty involved. At that point in time, once we're a clinically valid test, you can purchase the test and then to get the CPT, you tend to have to get two, three, four publications under your belts. And that is a lengthy process. That could be years to get a CPT code.

Mimi:
Oh, wow. Now, are you actually looking for people to submit their specimen for clinical trials?

Dr. Regina Lamendella:
Yes. If people are interested in submitting a sample and becoming part of our IRB approved study, we essentially have a consent form that we'd walk through. Our test kits, which I can show you a picture of at some point, are barcoded. So literally you can scan it with your phone. It'll pull up that consent form. You could read through it, sign off on it and become part of our IRB approved study.

Mimi:
That's great. If anyone's listening wants to do that, where would they go?

Dr. Regina Lamendella:
It'd probably be best because I'm a executive VP for our research and development. They can contact me via email. That's ReginaLamendella@CSIdx.com.

Mimi:
Okay. And I'll put that in the notes. For anybody who's listening, I'll have her email in the notes too, as well to contact you, that's great. Also, I notice a lot of times people who have Lyme also have parasites or mold. Does that get picked up in these tests at all?

Dr. Regina Lamendella:
Yes. That's a great point, Mimi, because it's an untargeted test. We have over 10,000 different viral, bacterial and eukaryotic pathogen. So yes, we would absolutely capture parasites, we would capture fungi. Literally anything that has RNA in it, we would be able to capture with our test system.

Mimi:
That's great. I think Gary spoke to me about this prior, but once you have the test, I know this is a case with the other two protocols that you're doing for sepsis and stuff like that. You can target exactly what antibiotics to help with that sepsis. Is that the same thing for the Lyme?

Dr. Regina Lamendella:
Yes. Because we are targeting the RNA from the entire pathogen, we also get a slew of all the virulence genes. So those are genes that make organisms toxic, et cetera. We would get their antimicrobial resistance profile. So we know antimicrobial resistance is a huge issue facing the field of medicine because bugs are constantly learning, they're constantly evolving, they're constantly changing over time. That's another beautiful facet to the CSI-Dx test is that because it's comprehensive and untargeted, we're keeping up real time with pathogen evolution, which is really important when you think about Lyme disease and other tick borne associated diseases. We know that they are expanding their geographic range, expanding their temporal range due to global climate change, et cetera. These pathogens are constantly changing their DNA and their RNA. And so the beauty of CSI-Dx is that we don't have to constantly redesign our tests like the antibody-based test, the PCR-based test, they're constantly happening to redesign because the pathogens are changing, their target is changing.

Mimi:
Is there other treatments besides the antibiotics that you would recommend from your diagnostics, if it's herbals?

Dr. Regina Lamendella:
Yeah. So being a molecular microbiologist, I'm not a trained physician, so I'd be a little leery to recommend any of those other therapies. However, I know that obviously there are some commonly used antibiotics that get prescribed and they work most of the time. But 10, 20% of the time they might not and that infection lingers and goes chronic. And I'd love to see, I know there's a lot of federal funding out there to investigate other therapeutics. So really I'm excited to see what the literature tells us for those interventions.

Mimi:
But as far as specifically, like for your microbiome or anything, is there anything from your test, like if I were to get tested and you tell me I have Borrelia, whatever, would you be able to say, okay, but also, your microbiome is off and you should be taking this or that. Is there anything specific that you also are recommending with the test or is it come back just strictly like you have Borrelia, you have Bartonella.

Dr. Regina Lamendella:
That's a great question. Yeah. Not only will we give the physicians the list of pathogens that might be causing the disease, our hope in the 2.0 version of the test is to give that antimicrobial resistance gene profile, because that could help direct physicians to what antibiotics not to use because they may have been exposed to these antibiotics in the past and their microbiome might be resistant to them. So we'll get there, we're just not there quite yet.

Mimi:
That's a long term goal. That's great. So what else have we not covered that we should be letting everybody know about CSI and what you guys are working on?

Dr. Regina Lamendella:
Yeah. So I would say the exciting thing about our company is that we have such a group of individuals here, from bioinformaticists, to molecular biologists, to microbiologists. We have the best of the best in terms of our team. And we're the only fully vertically integrated company of our kind. So we have all of the wet laboratory processing is done on site. So we have all the robotics, high throughput sequencers. We also have our entire bioinformatics processing is occurring in-house. That bioinformatics is just a fancy word for data analysis, right? We have to take those RNA sequences, which are like little thumbprints for telling us which bugs are in a sample. And we have to compare them to a database to identify who they are. And so we do all that processing in house as well. And so we have patents pending with about 50 claims each that protect the wet lab tower, as well as the dry lab, the data analysis tower.

Dr. Regina Lamendella:
And we're the one stop shop, right? We have a LIM system, a lab information management system that wraps around our entire process from when we receive a sample, it gets scanned into our system and is tracked through the entire wet lab and bioinformatics process all the way through closing that loop, which is to get the report back to the ordering physician. So all that is done in-house, they're aren't many laboratories. There are no laboratories, to my knowledge, of this kind, doing the RNA sequencing that we're doing. The other incredible long term value, I would say in CSI is our proprietary databases that are literally keeping up with, I call it a living database because we're constantly repopulating those databases with changing pathogens. We see this happening with COVID 19, right? We see SARS-CoV-2, it's genome is evolving over time. It's learning from us, right?

Dr. Regina Lamendella:
That's how pathogens work. That's why they've been around for 3.8 billion years, right? They're very good at adapting and evolving. And so that repository, that database, is going to be mission critical to pharmaceutical development, additional drug development and therapies. The other thing I think's really exciting about sequencing all of these tick born pathogens is that I think we're going to learn a lot in terms of pathogenesis. The mechanism by which these tick born pathogens make us sick is really largely unknown. And so I think the data that we're generating is really going to help research scientists understand how these bugs are causing infection, how they're hiding out in our system.

Mimi:
I know this is a little off topic, but I'm just curious, because I know this is an issue that I think a little bit tension in the Lyme world, but have you seen from your research thus far, and if you don't want to say it, because it's too controversial that's fine, that the Lyme disease can come through either sexually or gestationally or is it strictly through a tick?

Dr. Regina Lamendella:
Yeah, so I think the most common mechanism is likely through the direct tick bite. However, there have been, to my knowledge, documented published studies on some rare cases of things passing from mom to baby.

Mimi:
Yep.

Dr. Regina Lamendella:
It doesn't surprise me as a microbiologist understanding a little bit about the structure and function of Borrelia. They're a spirochete, so they're these little cork screws, right? So they can weasel their way into really small places. We know they're hiding out in our joints, we know they can make it all the way to the brain. So it wouldn't surprise me that they can get across from mom to the fetus.

Mimi:
But you wouldn't be able to tell from your study or your diagnostics, like where it came from? Like, Hey, this came from the mother or this came...you know, sometimes with cancer, you can find out exactly where it came from as far as like even though it's in your liver, it started in your breast or whatever. You wouldn't be able to figure out from your diagnostics where?

Dr. Regina Lamendella:
Now I'm purely speculating, but knowing about RNA sequencing and a lot of what we do is pattern matching. We match this RNA sequence to this RNA sequence. And so you can do source tracking with sequence data. So it's certainly possible.

Mimi:
That's what I was curious when you're saying with all the data that you're going to be collecting, eventually you wonder if you will be able to figure out where it's coming from.

Dr. Regina Lamendella:
Exactly. Yeah. We have a national science foundation, SBIR, they're a small business innovation grant. We have a grant out right now that's under review to do just that. We're actually trying to sequence all of the organisms that live in the tick to help make our databases even more robust. And so over time, as we accumulate that data, and we're going to be sampling ticks from as many of the 50 states as we can partnering with a variety of different institutions. And the idea being just what you're saying, Mimi, can we source identify, can we source track where these organisms are coming from? And that's where the database is mission critical.

Mimi:
Gina, I know that with this technology you could have studied cancer. There so many other illnesses or whatever you guys could have taken on? Why did you guys take on Lyme?

Dr. Regina Lamendella:
Yeah, so we took Lyme and two other very challenging disease states because of how much people are suffering. And we know in our home state here in Pennsylvania, we are usually the number one state for newly diagnosed Lyme infections. And so we wanted to be as impactful as possible. And the field is suffering, Lyme diagnostics are suffering from lack of good diagnostics. I mean the whole debate of over does chronic Lyme even exist, that's the example that because we don't have a good clinical definition for chronic Lyme, some physicians are ignoring it. And so I think this is where diagnostic CSI can help change the game in terms of saying, okay, let's see what we see in this untargeted nature. And even if it isn't chronic Lyme, the beauty of this test is maybe we detect other organisms that might be plaguing an individual.

Dr. Regina Lamendella:
So yeah, we decided to start with Lyme. We know that in addition, it's a huge burden on our healthcare system and our workforce. I think the estimates are three billion in direct costs to our healthcare system and 50 to 100 billion in indirect costs, much of which may coming from chronic Lyme. I've seen a lot of individuals in working with physician over the years that have basically been rendered incapable of going back to work. And so you think about all that trickle down effect. So it just made a lot of sense for us to focus on a disease state that doesn't have a good gold standard and see if we can make an impact.

Mimi:
That's great. It's amazing how there's so many people that probably don't even realize they have Lyme, right? There's a lot of ALS patients or MS patients that realize it could have started from Lyme and has progressed.

Dr. Regina Lamendella:
Yeah. And that quality of life, I think there's some surveys out there that show chronic Lyme disease that the patients suffer a worse quality of life than most other illnesses like congestive heart failure, diabetes, MS, arthritis. Over 70% of the patients with chronic Lyme report fair or poor health. And so, like I said, that trumps all the other chronic disease states that we know about. And so yeah, if we can make an impact by getting a physician a good answer early on, when it's in the acute phase, then it doesn't have to go chronic. And to get people answers that are plagued by chronic disease. It's just devastating.

Mimi:
So if anyone wants to learn more, you can go to CSIdx.com. And then if you want to be a part of the clinical trial, you will email Gina, and I will include her email in the notes for the podcast. But this has been amazing. I really appreciate your time. Is there any other things that we have not covered that you wish to share?

Dr. Regina Lamendella:
This might be a little off topic, but I always like to, the mentor in me, it's the research mentor and professor in me. To any of those female scientists out there, don't be part of what I call the leaky pipeline for female scientists. So we know that roughly half of our biology students are female, half are male. And then by the time we get to the professional side of things, that balance of 50/50 goes way down. And I almost even succumbed to this after a very negative experience with unsupportive supervisors during my graduate work. And I think it's really important to find good role models out there and surround yourself by inspiration and support. I had the fortune of landing an awesome postdoc at Berkeley under the supervision of Dr. Janet Jansson. And she was just this example for me of the work-life balance and success. And you can have it all. And so for any of those young budding female scientists out there, just keep on keeping on.

Mimi:
That's great. Well, thank you so much, Gina. I really appreciate your time and I'm excited for what's to come and what you guys are doing with CSI.

Dr. Regina Lamendella:
Thank you so much for the opportunity, Mimi.

Mimi:
Each week, I will bring you different voices from the wellness community so that they can share how they help their clients heal. You will come away with tips and strategies to help you get your life back. Thank you so much for coming on and I am so happy you are here. Subscribe now and tune in next week. If you want to learn how I detox and you want to check out my detox for Lyme checklist, go to Lyme360.com/detoxchecklist. You can also join our community at Lyme 360 Warriors on Facebook and let's heal together. Thank you.