Gladden longevity — Episode #20

Speaker 1: Welcome to the Gladden Longevity Podcast with Dr. Jeffrey Gladden, MD, FACC, founder and CEO of Gladden Longevity. On this show, we want to answer three questions for you: How good can we be? How do we make 100 the new 30? And how do we live well beyond 120? We want to help you optimize your longevity, health, and human performance with impactful and actionable information. Now, here's today's episode of the Gladden Longevity Podcast.

The Gladden Longevity Podcast is provided for informational purposes only. It does not constitute medical advice. This content is not intended to be a substitute for a professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The use of any information and materials linked to this podcast is at the listener's own risk.

Dr. Jeffrey Gladden: Well, welcome, everybody to this edition of the Gladden Longevity Podcast. This is going to be a great show. I'm here with a fellow MD, Dian Ginsberg, who's a board certified OB/GYN that's also completed the A4M training and so is basically a boarded functional medicine physician as well. And today, we're going to be talking about a really interesting topic, which is young plasma. And we're all familiar with the story of parabiosis when an old mouse and a young mouse circulations were mixed. And in that context, the young mouse got old and the old mouse got young, so it led to a lot of things about young blood and things like that.

And then the Conboys at Berkeley, Irina and Michael Conboy, published some papers looking at using plasmapheresis, which is basically a technology that we have now in our clinic, but essentially what it does is it removes plasma from an individual and replaces it with saline and albumin. And they've been showing some benefits with regards to different neurological diseases. In the mouse model, it actually rebooted stem cell function across all three different germ cell layers, which means the endoderm, mesoderm, and ectoderm. So all the different organ systems, muscle, skin, all that stuff was being rebooted to varying degrees. And so the question becomes, really, what is the role of young plasma? They started to raise that question, is young blood even necessary? Does young plasma really have a benefit?

So these are some things that we'll jump into today with Dian. But before we jump into the science and actually what we're doing, Dian, talk to us a little bit... First off, welcome to the podcast. It's great to have you here.

Dr. Dian Ginsberg: Thank you so much. I appreciate you having me.

Dr. Jeffrey Gladden: Yeah, absolutely. And then, why don't you tell us a little bit about your story, how you got to be where you are today, writing grants related to young plasma, and things like that?

Dr. Dian Ginsberg: So I am a board certified OB/GYN, did that for many, many years. And I tell everybody that probably my transition to the functional space and understanding neurological changes came from my kids. I was an overworked, up-all-night resident, wound up delivering my two boys, and neither of them had language till about three or four years old, and my youngest one actually close to five years old. I was told that my kids were [inaudible 00:03:27] mentally retarded and would never talk.

And at the same time, I saw the women's health initiative come out where the hormone replacement therapy was now told that women were going to get cancer. So I had women throwing their hormones out, I had kids not talking. And the American Academy of Anti-Aging functional medicine conference came up, talking about bioidentical hormones and ways to help the gut. And I found myself, 15 years ago, at that conference, brought the info home about the microbiome and neurological changes and how we are not what we think we are, and turned my kids' lives around.

They cleaned up their gut, fixed their circadian rhythms, and my big one is now about to graduate med school and my little one is in graduate school.

Dr. Jeffrey Gladden: Wow. Oh, outstanding.

Dr. Dian Ginsberg: So that functional space, it became my world. And I brought it into my OB/GYN business and started to help with fertility, and gut support, and patients that had all kinds of neurological problems that were cured even seeing me just for OB/GYN.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: And then about four years ago, three years ago, a well-off gentleman that was my patient decided to get more involved in the real longevity space, and he was fascinated with the concept at that point of what younger factors could do to the aging process. And Harvard had just come out with the GDF11 studies and the Conboys, like you talked about, were doing the parabiosis. And we wound up getting involved with a lab that utilized or collected plasma with young factors, so age. The kids between 18 and 25 would donate their plasma. And we used that to infuse into patients with Parkinson's disease and they started to get better. And then they-

Dr. Jeffrey Gladden: So let me just back up for a second. So first off, kudos on cracking the code for your kids, right? I mean, that's got to be massive.

Dr. Dian Ginsberg: It was massive. It's massive.

Dr. Jeffrey Gladden: Yeah. Massive, right? I mean, it just changes everybody's life. So nice to hear they're doing so well, grad school, the whole thing. And then you have this, we'll call it, financially wealthy individual. Now, was he struggling with Parkinson's or no?

Dr. Dian Ginsberg: No, no. What happened is, is I think if you look at a lot of these really, really well-off, rich people, they've climbed, as you know, the hours we spend in medicine, the same thing that they spend building their business, and he got very sick.

Dr. Jeffrey Gladden: Why-

Dr. Dian Ginsberg: And he wound up finding a functional medicine doc that got him better, so the supplements and the concept of understanding your gut and your body, I think, turned him around. And so he went, "I want to do something epic. I want to open a longevity center."

In that case, we looked at a whole bunch of different things, and plasma, at the time, was really, really in the news. And the connection that we found, the person that owns the lab, his mother died of Parkinson's.

Dr. Jeffrey Gladden: Got it. I see.

Dr. Dian Ginsberg: But they had been using plasma on just everything random. They said, "Hey, let's start to use the young plasma," and they hung it on somebody that had diabetes and that got better, and another person, their eyesight got better. They had been using it just on individual people, seeing a bunch of different, amazing changes that almost aren't documented.

Dr. Jeffrey Gladden: So let's just make this clear for the audience what we're talking about here. So a young person, 18 to 25 or 18 to 24, whatever, really a college student, if you will, or somebody that's maybe in grad school, is donating plasma and it needs to be sex-specific.

Dr. Dian Ginsberg: Correct.

Dr. Jeffrey Gladden: So, a female is going to donate plasma and a female is going to receive it and, also, blood type is important.

Dr. Dian Ginsberg: Correct.

Dr. Jeffrey Gladden: If you're O, if you're AB, if you're A, if you're B, important to get that right as well. And then the plus and minus factors of blood typing don't really seem to come into account here; if you're O positive or O negative, that doesn't really seem to matter.

But nonetheless, you have young people that are donating their blood. You have a recipient on the other end, basically, the same sex, same blood type. And so what's happening? You're just running in how much plasma into this recipient here?

Dr. Dian Ginsberg: Approximately a liter.

Dr. Jeffrey Gladden: Approximately a liter, okay. And are you taking anything out, or you're just putting in?

Dr. Dian Ginsberg: Initially, no. Initially, a few years ago, when we started to use more of it on patients, it was just a straight about a liter in.

Dr. Jeffrey Gladden: Okay.

Okay. So about a liter in, so that's a fair amount. That's a pretty good volume load, quite honestly, for somebody to get a liter. It's one thing to get a liter of saline, it's another thing to get a liter of plasma, which has lots of proteins in it and other factors which are going to increase the extracellular volume, if you will, or the intravascular volume to some extent.

So when you were doing that, were you screening people for any kind of issues with regards to volume overload? There's TACO and there's TRALI and things like that that can happen. These are transfusion-related cardiovascular overload or transfusion-related acute lung injury, things like that. Were you monitoring for those kinds of things, or did you see any of that?

Dr. Dian Ginsberg: Yeah, we saw none of that. And I think the two things, so all the blood is HLA-checked, where it minimizes to zero the TRALI for the immune reaction, and it is run so slowly that we have had no problems.

Dr. Jeffrey Gladden: Okay.

Dr. Dian Ginsberg: Some of the original studies, I know, that were done in Stanford, what they did is they ran 250 CCs every week. And I think their theory initially was kind of gently go in and then also see, do you kind of pee your bad stuff out and then hang the new stuff in?

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: But here, just for patient convenience too, the liter seemed to be what we went with and we didn't see any problems.

Dr. Jeffrey Gladden: And over what period of time were you infusing the liter?

Dr. Dian Ginsberg: About two to three hours.

Dr. Jeffrey Gladden: Okay, so that's a pretty slow rate, quite honestly.

Dr. Dian Ginsberg: Oh, yeah. Yeah, checking blood pressure...

Dr. Jeffrey Gladden: I mean, just so the audience understands, you can run in a liter of saline in 30 minutes on somebody pretty easily, right? So to take three hours is really giving the body time to assimilate that volume if you will. Okay, so that's interesting. So you didn't see any reactions.

And then it sounds like people were just... And maybe you were involved with this. Are you administering it yourself also? Is it part of what you do, or is it that you're more in the center of the research piece? How does that work?

Dr. Dian Ginsberg: I'm more in the research piece of it.

Dr. Jeffrey Gladden: Okay. So you're doing the research. So in the clinics where they were infusing this, they were essentially trying it for different indications, like diabetes or dementia or what other... What's the spectrum of things that people were trying it for, do you have a sense for that?

Dr. Dian Ginsberg: Well, I think it wasn't even just a black and white, did they have a medical problem? I think as the research started to come out where maintaining healthy aging started to become more and more popular, it was, "Okay, I don't feel as good. My eyesight's going a little bit. I've got a little bit of eczema. My aches and pains bother me. Maybe my blood sugar's a little dysregulated," so there were a lot of people that wound up getting plasma infusions for that. And then they found, "Wow, I'm sleeping better, and my hair is growing better, and my weight's coming down," and that's really was the bigger step of it initially as opposed to, "I have a major problem." But then there were people that had issues of chronic fatigue that just couldn't get better, and blood sugar dysregulation, and they were on a bunch of medications, and those people significantly saw improvement also. So I think there was just a huge, wide range of where the infusions went.

Dr. Jeffrey Gladden: Okay. And so there was a study done on Parkinson's at Stanford that was published. And I read that study, it's pretty interesting. Do you want to walk us through that a little bit?

Dr. Dian Ginsberg: Well, so most of what I've seen, and tell me the published study you were thinking of, because I saw the Stanford Alzheimer's study that they called a safety study. The Parkinson's data-

Dr. Jeffrey Gladden: Yes, let me pull it up for you here.

Dr. Dian Ginsberg: The Parkinson's data that I saw, they did this study, but the actual data that came out, they saw-

Dr. Jeffrey Gladden: There's a safety... Yeah, there's a Safety of Plasma Infusions in Parkinson's Disease, that was in 2020, and I read that.

Dr. Dian Ginsberg: Correct.

Dr. Jeffrey Gladden: And then there was another one in 2018, it looks like, that had to do with safety, tolerability. So both of-

Dr. Dian Ginsberg: They were safety, yeah.

Dr. Jeffrey Gladden: Yeah, they were both safety studies.

Dr. Dian Ginsberg: Yeah, okay.

Dr. Jeffrey Gladden: Yeah.

Dr. Dian Ginsberg: So that I'm familiar with. I'm sorry, I thought I wanted to make sure I didn't miss one that saw an outcome.

Dr. Jeffrey Gladden: Yeah.

Dr. Dian Ginsberg: So, I was a little confused about why they would do that. Because as an OB/GYN, I pushed a lot of plasma into a lot of people over 25 years very rapidly. I'm sure in cardiology you saw that also in the hospital. So I was a little confused about why they would do a safety study because we know plasma is safe.

Dr. Jeffrey Gladden: Yeah.

Dr. Dian Ginsberg: We know from the FDA data every year it's safe. So I haven't seen anything that looked at outcome until we did our study.

Dr. Jeffrey Gladden: Got it. Yeah, I've got a-

Dr. Dian Ginsberg: Which, to me, is what's key.

Dr. Jeffrey Gladden: I've got another paper here that's actually... It's not from Stanford per se, but it's actually talking about the use of the young plasma in Parkinson's disease, and there were 22 patients enrolled, etc., etc. So anyway, there's some building evidence that this is safe.

Dr. Dian Ginsberg: Yes.

Dr. Jeffrey Gladden: And then what have you noticed in terms of the benefits, let's say, for Parkinson's?

Dr. Dian Ginsberg: So, what we did is, I'd seen so much in the rats, right? Everybody's hanging this stuff on rats, and we know plasma's safe in people. I saw it for 25 years. We see it every day in the unit, every day.

Dr. Jeffrey Gladden: Yeah.

Dr. Dian Ginsberg: So, what we did is we took 20 people with Parkinson's, 10 got B6, 10 got plasma. We had two neurologists working with the patients and they did UPDRS scores, the Parkinson's wellness score, if you would, the state of being, and cognition, and motor. And the patients were blinded and the neurologists were blinded. And what we found was significant increases, or improvement, I should say, increased, better state of being, in the Parkinson's patients that got the plasma relative to the placebo.

Dr. Jeffrey Gladden: Okay.

Dr. Dian Ginsberg: We also did a Stanford Presenteeism score, quality of life, and that got better. So the patients that got the plasma got better.

Dr. Jeffrey Gladden: So just so we're clear and people understand what we're talking about, so when people have Parkinson's, it's a motor neuron disorder, really, that comes from the substantia nigra, and there's really a lack of dopamine signaling that occurs there. And people get stiff, they have a hard time walking, they lose their balance, their face becomes... It's almost like they're wearing a mask, is how it's described, where they don't have a lot of facial expression. Their voice gets weak.

Dr. Dian Ginsberg: And there's a bad... There's a cognitive, there's like an "I don't care about life," and a depression, which I think is also underappreciated.

Dr. Jeffrey Gladden: Appreciated, yes, I think that's exactly right. And people do become depressed, but there is also cognition issues and there can be a dementia associated with it as well. And Lewy bodies can sometimes be super imposed.

So this is a neurological disorder that affects the brain, but it has a systemic component, and so there are lots of different things that you can look at in a patient and see if they're improving or not. Obviously, the pill tremor in the hand is probably the classic one, but there are a lot of these other features as well, where you can watch somebody's gait, you can watch them walk, and you can look and see if they can smile, and you can do all these kinds of assessments. So just so the audience understands what Dr. Ginsburg is talking about here with these assessments is they're looking at those parameters.

And so when you were showing that there was significant improvement, what were these people doing? Are there videos of these people before having a hard time getting out of a chair and now they're popping up and walking around, or what are you actually seeing?

Dr. Dian Ginsberg: I think what you would see is the neurologist would do their exam. So they would come in, like zero, and the neurologist would do their evaluation. And then what would happen is at a one-month and three months and six months, the evaluation that the neurologist would do and the patient and the partner would describe were significantly different. The neurologist would see an improvement in the tremor, but the patient would say, "My sleep is improved. My motivation is better." Because one of the full parameters that you follow is activities of daily living.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: So, there was a significant improvement there.

Dr. Jeffrey Gladden: So, let me just ask you this. So was all this benefit the result of a single infusion, or were they getting infusions of a liter of plasma every so often, or what was actually happening?

Dr. Dian Ginsberg: So, we did a 0.0, they got one liter, a day off, and another liter. So it was a two-liter infusion, and then followed for six months.

Dr. Jeffrey Gladden: Okay. So a single time, really a single episode, over two days... Well, three days, I guess, of two liters of plasma, and then they just go from there.

Dr. Dian Ginsberg: Right. Correct.

Dr. Jeffrey Gladden: Okay, well, that's fascinating. And there were no other interventions made, I take it. Did they decrease their Parkinson's medications at all? Were they able to decrease those or anything?

Dr. Dian Ginsberg: I don't think that... Since it was only six months, we wanted a kind of an end point to publish it. They stayed on their same meds and the improvement was starting to come. So I don't know that their neurologists were quite ready to decrease the meds at that point.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: I think it was probably too short. It would be nice to do it more ongoing for two or three years.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: And we're even at a point where the question is, well, should you do it once every month or should you do it... So it's variable what the optimum is. But what this was, was a really prelim study to turn around and say, "How can we finally just quantify a starting point for something we can do?"

Dr. Jeffrey Gladden: Yeah, exactly. So this is one technique. There's another technique that can be done with plasmapheresis. So when I started the conversation, I was talking about being able to remove plasma and then replacing it with albumin and saline as a way of actually extracting out negative factors, if you will. And one of the things that we're interested in at Gladden Longevity is combining those two approaches, where you actually remove the old factors and then the idea would be to maybe put back a little bit of albumin just to make sure everything's working the way you want it, and then actually, instead of using albumin, using young plasma and being able to infuse maybe two liters, or maybe even a little bit over two liters, for a given individual and see if there might be a better benefit. And that way, you might get your two liters in one sitting as opposed to spread out over three days kind of thing. So just so the audience understands that there are a range of things being done here.

And then the other thing just to point out is that Dobri Kiprov has done and published a study in Alzheimer's patients, kind of earlier Alzheimer's, where they were just doing plasmapheresis, just removing the old plasma, replacing it with albumin and saline, and they showed some stabilization and a decrease in the rate of progression in Alzheimer's patients with that.

Dr. Dian Ginsberg: Alzheimer's.

Dr. Jeffrey Gladden: When I read the paper, they didn't really show reversal, per se. In other words, both sides of the equation seem to have a benefit here, removing the old stuff and maybe putting in the young stuff. That's the point I'm trying to make.

So where are you now with your whole... You're writing grants, you're doing things, what are you focused on now with regards to the young plasma?

Dr. Dian Ginsberg: I think we don't know the answer of what's best, right? So what we're trying to do is figure that out.

Dr. Jeffrey Gladden: Mm-hmm.

Dr. Dian Ginsberg: Now, I think one of the big problems we had, even with just Parkinson's, is the UPDRS score, the score that neurologists use to judge where the patients are, is fairly subjective, so there was not a lot of objective data. So there's a company that we're working with now called TruDiagnostic that does aging... I know you're familiar with them.

... Does aging clocks. For me, the concept is figure out what [inaudible 00:21:30] marker that's a little more black and white that we can use to show some kind of improvement. And I know in the recent Horvath paper, it was tough because they showed that epigenetic changes don't necessarily jive with cellular changes, and so none of the clocks are perfect and none of the blood markers are perfect, so. we're sort of in a murky place.

Dr. Jeffrey Gladden: That's right.

Dr. Dian Ginsberg: But what we'd like to do is put together laboratory data with clinical findings with different options.

When you look at the big pheresis, I know you do this in your office, everybody can't tolerate that. It's a tough procedure. Even the AMBAR, the Alzheimer's study they did, there were people that needed chest tubes and got infected. And older people sometimes can't tolerate that, so the other option we have is something we call a minimi, where you do a very simple peripheral removal of one liter of old plasma and put a liter of young plasma back in. And maybe doing that over time will help.

So with the newest grant that we've written, which I think is really cool, is looking at 40 patients, but we're not limited to what they do. So one patient may do three minimis, and somebody else may do, say, a big pheresis in your office, and somebody else may do a number of different pheresises. So what I'd like to do is then take those people, we're going to do clinical testing, grip testing and strength, and standing from a chair and standing from the floor, and pair that with the TruDiagnostic, the epigenetic clocks, and pair that with hemoglobin A1C and Cystistatin in some of the basic labs and see what comes out the other end.

Dr. Jeffrey Gladden: Right. Yeah, and I think that's the right direction to be going. I think the audience has heard me talk about the fact that we're all a mosaic of ages, right?

Dr. Dian Ginsberg: Mm-hmm.

Dr. Jeffrey Gladden: And so, we all have many, many clocks running, if you will. And we know that the Horvath clock, the DNA methylation clock, which is really what true age is measuring is DNA methylation clock, is a good clock for predicting age. It's also would be interesting to look at, there's a DunedinPACE, that's D-U-N-E-I-N-P-A-C-E, that was developed out of Duke, utilizing the clock to show what the rate of aging is. And it would be interesting to see if with the young plasma you're actually affecting the rate of aging as well as what the epigenetic age is.

Dr. Dian Ginsberg: We actually did that. We did that on two people.

Dr. Jeffrey Gladden: Okay.

Dr. Dian Ginsberg: So, our prelim two people, so we did it on a 70-year-old and a 55-year-old. So we did their baseline. We did the advanced proteomics at TruDiagnostic, and then we did a one-month and then... Oh, I did a two-week on one, then a one-month, and then we're waiting on the two months. And actually, our 70-year-old was fascinating. He got a big hormetic reaction. So what that means for our audience is that the system gets stressed, kind of like people talk about why raising your heart rate works and why cold and hot and all that works, so you stress the system a little and then it recovers healthier.

Dr. Jeffrey Gladden: Okay. Right.

Dr. Dian Ginsberg: So, he got a bit... At two weeks, we saw in the rate of aging, the Dunedin clock, and the GrimAge... So the GrimAge clock is time to death, so it got a little worse. But then at one month, his GrimAge went back five years from his baseline.

Dr. Jeffrey Gladden: Yeah, yeah.

Dr. Dian Ginsberg: And our second person had done a three-liter transfusion pheresis before he got his plasma. He had less of a hormetic reaction and he got a little bit of a drop in his GrimAge, and also had a decrease in his rate of aging. So we're definitely seeing improvement in our prelim people that we've done.

Dr. Jeffrey Gladden: That's fascinating. We're in the middle of measuring similar things, and actually more things quite honestly. But what we have noticed is that there is a stress to undergoing the procedure. And one of the things that we follow for people in our world, are always wearing whoops or Oura rings or Apple watches or whatever, so we're learning that their heart rate variabilities are actually going down initially. And we know that that's a measure of stress; it's a balance between the sympathetic nervous system, the parasympathetic nervous system. When the body is stressed, either from exercise or a sauna or whatever, there's this hormetic stress, which is a healthy stress, not enough to really damage you, but enough to stress the system, so you come back stronger. We're seeing that the heart rate variability is staying suppressed for several weeks before it starts to come back up again, which is kind of in line with what you're saying. And we're also measuring lots of different clocks, if you will, besides just the DNA methylation stuff, so it'll be interesting for us to compare notes on some of that.

So one of the things I think that people in the audience are wondering about is transfusions. Well, isn't that risky from the standpoint of, "Am I going to get HIV? Is there hepatitis C, I'm going to get?" Do you want to talk a little bit about how this blood is screened? These are young people and that kind of thing, do you want to talk about the safety relative to that?

Dr. Dian Ginsberg: Yes. So basically what happens is that each young student that comes in fills out a whole questionnaire on their medical history. And not only do they get the same screening that, say, the Red Cross would screen, right? Because what does the Red Cross do? They do basic screening and then they dump all the plasma into one big vat. And if you wind up in an accident, you get what you get.

Dr. Jeffrey Gladden: Yeah.

Dr. Dian Ginsberg: So here, they go through that screening, but including the basic test, there's another five or six plus the HLA testing that we do. So it's in depth, what the Red Cross does plus above and beyond that. Then what happens is, is the plasma's held, the student's brought back 30 days later, same testing done again, and then not until that's still negative is the plasma released.

Dr. Jeffrey Gladden: Got it. Yeah, so really, it's a much more fastidious approach than what the Red Cross would be taking relative to normal blood products.

Dr. Dian Ginsberg: Oh, yes. Oh, yes.

Dr. Jeffrey Gladden: And do you want to speak a little bit to the HLA typing, the impact of doing that kind of typing?

Dr. Dian Ginsberg: Well, I think probably for kind of a global picture is that an inflammatory reaction is what's going to hurt you. So when you get plasma or blood or whatever we receive as a patient when we're sick, the body will react to a foreign substance. So what happens is... That's right, that's why we match the type, and that's why we match the RH when you give blood, because the body's going to turn around and say, "What is this?" And react to it. And your immune system... It's almost like COVID, right? People, it wasn't the virus, they died of their own immune system attacking themselves to try to heal.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: So, the immune system's very powerful. A lot of people have seen that a little bit in a histamine reaction. If you ever have an allergic reaction to anything, your body, your heart rate goes up, your blood vessels dilate, you get red, your immune system goes a little crazy trying to protect you. Well, what'll happen is, is that if this antigen is in the blood... And it tends to develop a little more commonly in female blood that's been pregnant, because of the baby. So if the baby’s blood type is different than the mom and there's a cross in the pregnancy, the mom's body will react to the baby and she'll have these antibodies in there that can be a little bit sticky if it winds up in somebody else.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: So, if you get a transfusion with somebody that's got those HLA antibodies in, they will attack and create that inflammatory reaction, just like a histamine reaction gone wild. If anybody's ever seen anybody get a bee sting or have an allergic reaction to peanuts, that'll happen. So that's the TRALI that they talk about, just the fluid builds up everywhere. So as long as the plasma is HLA-tested and there's no HLA in there, the chance of any kind of real reaction is close to zero.

And even the FDA numbers, I think they had maybe four TRALI reactions, even in the plasma that they do in all of 2019. So people talk about anaphylactic or allergic reactions or plasma not being safe, but it's safe. It's probably safer than driving your car down the street.

Dr. Jeffrey Gladden: Yeah. No, it can be quite safe. And I think, to your point, just so the audience understands, TRALI is this transfusion-related acute lung injury is the acronym. And what happens is inflammation in the lungs can cause fluid accumulation in the lungs, so it's kind of analogous to something we would call acute respiratory distress syndrome where the lung can fill up with fluid.

And so as a physician, if you're going to be involved with anything, you want to make sure that you're minimizing any risk for anybody that might be involved with this, so minimizing the risk for TRALI, making sure that this is HLA-negative, making sure that you're compatible with the blood type, etc., the sex type, all of that, to minimize all that risk.

Dr. Dian Ginsberg: Right.

Dr. Jeffrey Gladden: And then even without that, the incidence is so infinitesimally low, so we feel like the risk now would be even lower, if you will. So again, you can never say never in medicine, but the idea is that it would be very low.

Dr. Dian Ginsberg: And when I think about even my 25 years, I go back to the labor and delivery suite, like we talked about in the beginning. I mean, I can't even remember the last time I saw anybody have a horrible reaction to blood with the cells, much less than plasma.

Dr. Jeffrey Gladden: Right.

Dr. Dian Ginsberg: I mean, postpartum hemorrhage, I mean, they're putting blood into people at high volume.

Dr. Jeffrey Gladden: No, that's right. Oh, I know.

Dr. Dian Ginsberg: It's really screened and really safe.

Dr. Jeffrey Gladden: Yeah. No, that's right. And we see that all the time. And just so the audience understands this too, the reason that we're giving plasma, that she would be giving so much plasma is there's a lot of clotting factors there. So if she has a high risk pregnancy and somebody's bleeding, that sort of thing, pushing that plasma in is giving them more clotting factors to help stop the bleeding. That's really kind of what's going on there.

So do you want to talk a little bit further about what's going on with the research protocols that you're working on, the grants, now you're actually applying for grant funding for the studies and things like that?

Dr. Dian Ginsberg: Yes. So like I said, because we believe, as most everybody does, that the process of the disease of aging creates a lot of the diseases that we see. So our Parkinson's study was, "Okay, you have Parkinson's, what can we do to try to reverse it?" And I believe it's global, and we may go even higher and turn around and say, "Well, we know the microbiomes involved in Parkinson's, and we know lifestyle's involved," so there's angles we can go where we can work on the gut while we add the plasma. But I think the biggest thing we're looking for with our grants now is to be able to support as many different clinicians, I want to be able to give to clinics so they can recruit patients that have medical problems, non-medical problems, just a combination of everything, to support the expense of the pheresis and the plasma and the testing, to be able to see what happens and then who this can be optimally applied to.

We're working very, very closely, like I told you, with TruDiagnostic. And one of the things they said they can do is they'll be able to use the samples and pull apart the proteomics enough, or kind of the genetics, to where they can come up with, "Hey, these people got better, and this was their genetic profile. These people, they have more of a tendency to develop Parkinson's." So it might be cool to be able to say, "Well, now we see how these people got better," but then you can backtrack it and say, "Let's just do a simple TruDiagnostic on everybody. It's an easy blood test. And if you run this particular profile, you are a setup for Parkinson's," so you start getting treated when you're 50 or 40. And what you're doing is you're preventing that epigenetic drift, that change in the genes to send you down that pathway. And to me, that's real prevention.

Dr. Jeffrey Gladden: Yeah.

Dr. Dian Ginsberg: You don't wait till the horse is out of the barn, you lock the door first.

Dr. Jeffrey Gladden: That's right. Yeah, that's exactly right. Yeah, we're in the middle of doing a collaboration with a transcriptomics company to do a very similar thing across even a broader spectrum of things. Because, just so the audience understands, as you age, there's about 1,500 genes, basically 1,497, that have been shown to be either upregulated or downregulated. And so even though your genes stay fixed throughout your lifetime, your DNA doesn't change, the expression of that DNA does change with age. And so being able to, in our world, apply different technologies and kind of stack them together and sequence them together in certain ways, what we're really looking for, and what she's talking about here, is can we actually change the way in which your genes are being expressed? Can we actually change your genetics to be expressed more like a young person and less like an aging person or an older person? And that's really, I think, one of the holy grails of this whole thing of actually proving that we're actually turning back the clock, if you will, actually moving people in the right direction. Yeah.

Dr. Dian Ginsberg: Yeah, and again, I think that if you look at the aging world, everybody talks about, what's going to be left for our kids? The answer isn't to have a group of older people that they have to take care of, but to prevent them from getting sick in the first place. And when I think-