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Welcome to the Healthy Brain Toolbox. I'm Dr. Ken Sharlin, neurologist, speaker, author, and host for this show. In each episode, I interview influential people whose work impacts how we live and how we think. My guests are leaders in the health and fitness industry, physicians, scientists. Authors and public servants. Here, you'll find conversations that break down barriers, expand your horizons, and give you the tools you need to protect your health and nourish your aging brain.

Dr. Ken Sharlin: 0:39

For today's episode, I'm interviewing Dr. Noelle Patno, PhD. She's the Chief Science Officer at Bened Life. And she holds a BS, bachelor of Science in Chemical Engineering from Stanford University and earned both an MS and PhD degrees in molecular metabolism, nutrition, and translational science from the University of Chicago. Her career is focused on digestive health, the microbiome and immune function with extensive experience designing and overseeing clinical trials on probiotics, prebiotics, and psychobiotics. We're gonna learn about all of those today at Bened Life, she advances gut brain science through neuralli MP, a medical food delivering lactobacillus planetarium. PS128 a psychobiotic shown in preclinical studies to protect dopaminergic neurons. Improved coordination. And reduce neuroinflammation. Clinical research in Parkinson's patients has further demonstrated PS128 ability to improve motor function, reduced off time, and enhanced quality of life, make embedded life's work, a leading example of translating microbiome science into therapeutic strategies for neurological wellness. Dr. Patno, as we start the interview today, I wonder if you could share how your personal health journey and academic background really shaped your path to becoming the CSO at Bened Life.

Noelle Patno, PhD: 2:16

Sure. I was interested in math and science, which took me toward chemical engineering based on my experience with peers and mentors, and then. I actually had an experience during my work as an engineer on the job severe gut pain, which eventually I found out was colon cancer after emergency surgery. So that was pretty shocking at a young age to have colon cancer and it was fully surgically removed. I was recommended adjuvant chemotherapy. But I did my own research to find out that the benefit would've only been one to 6% increase in five year disease free survival.

Dr. Ken Sharlin: 3:03

Wow.

Noelle Patno, PhD: 3:04

So I went to multiple, alternative doctors, homeopathic, functional medicine, et cetera, I worked on my nutrition and supplementation for my personal health journey. I went back to school to get my PhD and then went into advancing research for nutritional supplements and nutritional approaches to chronic disease.

Dr. Ken Sharlin: 3:31

I take it you've had tremendous success with your personal journey and how you approach the colon cancer then helped.

Noelle Patno, PhD: 3:39

I have not had a recurrence for, let's see, it's going to be almost 15 years, which is really wonderful.

Dr. Ken Sharlin: 3:45

That is wonderful and congratulations and you know this is such an important message. For folks listening, we talk to people who have multiple sclerosis, who have, reversed their disease. I have cases of Alzheimer's where I can demonstrate objectively that folks have actually go from being biomarker positive to biomarker negative. And so it, the big picture message of whether we're talking about cancer, whether we're talking about neurodegenerative or neuroinflammatory disorders, that we have a lot more resources at our fingertips and we're led to believe that the tools out there the tools really are out there and while the drugs. The surgeries and the radiation and things like that are important. We don't wanna discount the role that they play. We also want folks to be aware that there are things that are in their control that they can do, and really integrate the best tools for them to get the best possible outcome.

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Dr. Ken Sharlin: 6:43

How does the current research describe the gut brain's axis role in Parkinson prevention and really what is the gut brain axis to begin with, how does that play into Parkinson's? Which, hey, Parkinson's, is a brain disease, right? So what does the gut even have to do with it?

Noelle Patno, PhD: 7:02

There's a lot of emerging research and for some time now that actually shows that Parkinson's disease may begin in the gut. People having symptoms even 10 years in the gut as something like constipation before being diagnosed with Parkinson's disease and the gut brain axis would encompass multiple routes of communication. Between the gut and the brain where can observe something like Parkinson's disease to actually travel from the gut to the brain. In some cases, I can give you examples of how mechanisms occur, from how the gut talks to the brain. Like we know the vagus nerve is a major one, connecting the gut to the brain and of those nerve fibers, and there's actually communicating that sensory, et cetera, information to the brain. Then there's obviously the blood circulation system, which could, we absorb so much through our gut. We have all our nutrition through the gut. the functional medicine world we talk about how disease begins in the gut. So we need to absorb all of the necessary nutrients we need to have good microbes in our gut to support. Not only metabolism, but also immune signaling and even nervous system signaling, which even relates to supporting dopamine levels in the brain, which you can see can impact Parkinson's disease, for example.

Dr. Ken Sharlin: 8:33

Yeah. Things like leaky gut, increased gut permeability with the release of at least parts of the bacterium that can be inflammatory. The Lipopolysaccharides into the, vascular system ultimately triggering an inflammatory response at the blood brain barrier level and then triggering an inflammatory reaction in the brain itself. And we've also read about, and heard about alpha synuclein the pathological protein, or at least in the context of Parkinson's, a pathological protein. It appears that can form in the gut, but ultimately find its way to the brain and then spread through the brain as I understand it, in a almost virus-like pattern from neuron to neuron.

Noelle Patno, PhD: 9:22

Yes, and preclinical studies have actually shown that Alpha-Synuclein, misfolding and aggregation starting in the gut, moving the vagus nerve to the brain. So it's not just a hypothesis, but also. Can be shown mechanistically in a preclinical study. Yeah.

Dr. Ken Sharlin: 9:39

Absolutely super important and really just begins for folks with this message of taking care of your gut if you wanna take care of your brain regardless, whether you have Parkinson's. And I believe there's some, been some other studies out there, a little bit contradictory sometimes in findings but still pointing strongly toward this gut brain connection and Parkinson's. I think it was an earlier. Somewhat older study looking at people who had gastric ulcers in an old approach to the treatment of gastric ulcers, which was to clip the vagus nerve. And then, thereby interfering with that gut brainin connection, if you will. That wasn't necessarily reason for doing the surgery. But in the end, the people who had these demise for peptic ulcer disease for gastric ulcers specifically had a lower incidence of Parkinson's. And then I think there've been some similar concept. Though not necessarily conclusive studies, some on both sides. Some saying yes, some saying no but related to appendectomy and Parkinson's, some of which suggest that perhaps the appendix is a reservoir of our gut microbiome, that if it gets disrupted. Then we can restore the microbiome in part through the appendix. But if it's removed and then there's disruption of the microbiome, we don't have that reserve. And so individuals were more likely to develop Parkinson's. On the other hand I've, I believe I'm aware of some papers as suggested that removal of the appendix seem, seemed to result in in increased risk of Parkinson's. Both ways, but nevertheless still ties in the gut and the brain pretty convincingly.

Noelle Patno, PhD: 11:24

Yes, definitely. But we don't want to to cut the vagus nerve to prevent Parkinson's

Dr. Ken Sharlin: 11:29

No. And to be clear, for the listeners or viewers, none of these were specifically related to Parkinson's. This was, treatment of acute appendicitis, to my knowledge, no longer performed surgical procedure to treat gastric ulcers. Now we, recognize the role of things like h pylori and treat with sort of a cocktail of antibiotics and other things that help to heal the digestive tract. Segueing into PS128 and kind of what is it? We, I'm sure first observations on any potential for a clinical benefit were observed in mouse models. Can you talk a little bit about, that preclinical evidence.

Noelle Patno, PhD: 12:10

Yes, there have been multiple studies pre-clinically showing that PS128. Or a plantarum. PS128 can help with the Parkinson's disease condition. in multiple. Examples. PS128 actually helped support the dopamine levels in the prefrontal cortex, striatum, and the midbrain. So those are involved in, not just motor function, but also there's learning memory in those d different parts of the brain. As the neurologist, I'm sure can tell us more about that part, but. Not only that, but also what the rotor rod test, the narrow beam test. There are videos showing the animals going across like a balance beam, for example. And then you see the normal condition can go across the balance beam that the disease condition has trouble, slower, less coordinated, might even almost fall off. Right? And then PS128 administered mouse is doing better. Maybe not quite as better as the mouse that doesn't have the Parkinson's disease condition, but it's able to get across in a better time and with more coordination. It. It was also compared against L-DOPA administered to these mice. And in some cases it was similar to the L-DOPA condition, but not in all cases. It wasn't quite as beneficial as the L-DOPA, which you wouldn't necessarily expect that L-DOPA is the drug that's actually delivering. The precursor so that you get the dopamine actually, whereas PS128 is going to be a little bit more indirect in acting from the gut to regulate that dopamine in the brain. And we think it happens through a variety of mechanisms. None of which are completely, fully elucidated. But one could be through modifying the gut microbiota. A another could be through modulating the immune response. So reducing peripheral inflammation, reducing the neuroinflammation, having a neuroprotective effect. And that was shown by reducing cytokines, not also, not only peripherally, but also in the brain. And there was also an interesting MicroRNA mediated potential mechanism, although it's not necessarily a primary mechanism. But it's also an interesting one that correlated with the gut bacteria change as well as the immune response, So when you think about microbes, like PS128, think about how people we're all living microorganisms. We can play multiple roles and we can do things in a variety of ways. Microbes also have multiple effects, like potentially strengthening the intestinal barrier, like you said, protecting them from leaky gut potentially changing metabolism. It's interesting that amino acid metabolism is sometimes altered in Parkinson's disease patients, even vitamin D being lower and other kinds of metabolic effects. Probiotics or gut microbes could also, like we've talked about earlier affect the vagus nerve. They could bind to the end of the vagus nerve. So there's many other ways to explore mechanisms, but that PS128 has an impact on the immune response which is one of the large, on impacts supporting those dopamine levels in the brain and then supporting that Parkinson's disease preclinical model we were talking about.

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Dr. Ken Sharlin: 17:33

Now I'm just curious, and again, just please, definitely correct me if I'm wrong, you know what we broadly call the microbiome consists of a variety of microbes, bacterium, viruses other, types of other species, microbial species, but in general, if we're just focusing, say, on bacteria there may be certain, it's kinda like a fingerprint where everyone to an extent has their own unique makeup of microbes in their gut. Although maybe as to use a broad term like Americans sort of standard American diet, perhaps we overlap perhaps more than maybe. Hunter gatherers in, in the heart of Africa or whatever, who have a completely different type of diet. But I guess what I'm getting to is many times in functional medicine we talk about restoring the gut, healing the gut, giving the gut what it needs. A lot of functional medicine. Say in contrast to regenerative or anti-aging medicine is really about that root cause. And so it's not necessarily about treating someone something so much as giving the body what it needs to restore that homeostatic balance. So my question then is with PS128. Where did this sort of come from? Is PS128 a sort of a typical member, if you will, of the gut microbiome? Or is this something that's exogenous and typical in nature, but not necessarily in the human gut?

Noelle Patno, PhD: 19:01

So if you look at gut microbiome studies in humans, l plantarum as a species is not necessarily super abundant. To answer that part of the question, PS128 is a strain of L plantarum. Came from a spontaneous fermentation of Taiwanese mustard greens. it was isolated from a unique batch of fermented greens. Spontaneous basically means it just, it fermented on its own. It wasn't driven by a starter culture or something like that. then what we do with probiotic candidates. like PS128 would be to screen it for different kinds of activity, immune activity other kinds of functions that are of interest. Obviously look at the genome for antibiotic resistance, violence factor producing genes, et cetera. Once it passed these safety tests. Then you put it into further studies, like the preclinical studies that I told you about, and then eventually the clinical study that we can talk about. PS128 came from affirmative food, but it's not available in fermented foods in general.

Dr. Ken Sharlin: 20:09

So was there a sort of an aha moment where someone said, oh my gosh, look at what, it's almost like the discovery, if you're familiar with, of rapamycin. Like there was, it's an interesting compound and obviously a separate discussion, but, that was found, it's a basically from a mold spore, and so there were sort of empirical in nature observations that led to the thought that perhaps this compound may have pharmacological benefit. And then, testing in preclinical settings before we put it in human beings. Was there that similar kind of, how did we stumble upon PS128 in the first place?

Noelle Patno, PhD: 20:49

So it was screened from hundreds and hundreds of other and they were looking for candidate probiotics with different activities and it stood out as having stronger immune activity in vitro studies. And I think what was really interesting from my perspective is that effect on the dopamine levels in the brain. So if you look at a review article on certain probiotics or really psychobiotics affecting brain neurotransmitters. It appears that PS128 may be the first documented probiotic to actually modulate dopamine levels in the brain. So I think that's a pretty unique, history.

Dr. Ken Sharlin: 21:26

we're just curious. We're using, do you know if the mouse models were MPTP models or what they were using for them.

Noelle Patno, PhD: 21:33

One of them. There's an neuralli TP induced Parkinson's disease model. There was a rotenone induced Parkinson's disease model, and then there was the Hemi Parkinson's one. So they basically induce half the side of the brain with and the other side is a control, which is a really interesting way to, look at the disease and healthy state at the same time.

Dr. Ken Sharlin: 21:53

That is cool. I don't think I've, I'm not familiar with that. Your own internal control,

Noelle Patno, PhD: 21:57

yeah.

Dr. Ken Sharlin: 21:58

And I get a lot of questions about stem cells. And in that world of research, there's some effort to perhaps use induced pluripotent stem cells that become dopaminergic neurons in the brain. If we could just implant them into the substantia nigra and grow projections to the striatum. Maybe we can reverse Parkinson's. I'm not a, I'm not that kind of researcher. I do clinical research, but the problem I have with that theory is that, Parkinson's is more than a dopamine disorder. And when we get down into root causes and look at PS128, not only does it have an impact in a positive way on dopamine, but I believe other neurotransmitter systems, is that correct?

Noelle Patno, PhD: 22:45

Yes. PS128 has been shown to support serotonin in certain parts of the brain and I believe BDNF. So the brain derived neurotropic factor. And there was also, I think, an influence on norepinephrine, but I think I need to double check that one for you. Those are some of the ones that have been studied that I can remember, and we can also look at others.

Dr. Ken Sharlin: 23:11

Yeah, so in other words, in a sense. We're dealing with some of the imbalances in Parkinson's in a much more global way. When we begin with the gut, when we think about PS128, and not just targeting dopamine, but targeting serotonin, potentially norepinephrine, you've brought up brain derived neuro neurotrophic factor, and I'm wondering if any of those preclinical studies have either done, I'm sure you've done posts on, on, on the brains of these mice and or other studies that have asked question if you're influencing BDNF, are you seeing some neuro regeneration in the mouse brain?

Noelle Patno, PhD: 23:52

I'm not quite sure about neurogeneration of that. I don't think that question has been asked yet. there's been the neuroprotection. Angle. Seeing that the disease progression slowed at least, or inhibited or prevented in that mouse model. But I think to really evaluate brain regeneration, we'd have to look at how would we wanna ask that question design a proper study around that. There, there's also been a study in Alzheimer's disease, but for regeneration. I would imagine looking at, are there more neurons? Are there, are we counting the neurons? I do know that there was a greater number of tracine oxalate stained neurons in some of the PS128 studied mice.

Dr. Ken Sharlin: 24:41

Yeah. And speaking of Alzheimer's, I believe BDNF is particularly concentrated in the hippocampal structures. And so would be very interesting. I know there are ways to, do cognitive studies, if you will, on mice. Obviously they're not doing the CDR some of boxes or whatever, but there are ways to assess impacts on cognitive function and it certainly would be very interesting to look at things like hippocampal volumes as well as putting quotation mark clinical behaviors that reflect changes in cognitive function over time using this probiotic.

Noelle Patno, PhD: 25:19

In the Alzheimer's disease model in the pre-clinically, did show that PS128 supported short-term memory learning and cognitive function in that. Clinical model. So that's pretty promising. We haven't taken PS128 into Alzheimer's disease in clinical studies yet, but obviously it's of interest because dopamine can affect memory learning and cognitive function. So based on that one clinical study with an Alzheimer's disease model.

Dr. Ken Sharlin: 25:46

Most definitely we do here at Sharlin Health and Neurology, a lot of also a lot of hormone optimization in postmenopausal women as well as, unfortunately, too many men, present with low very low testosterone. Some of them at a surprisingly young age. Obviously a diet and lifestyle phenomenon for the most part, although things like traumatic brain injury can play a major role. But that being said, one of the things I emphasize is that dopamine and learning and memory very much go hand in hand. And our patients definitely, report back that they are feeling sharper, more on their game. Obviously more energetic and focused, things like that when we optimize testosterone in particular for both men and women. And we know even in preclinical, not preclinical and empirical studies of. Humans in Parkinson's, at least in men, that there's been an, that there's often an abrupt drop in testosterone before the onset of motor symptoms in Parkinson's. The larger clinical trials have not been as successful in demonstrating a role for testosterone. But certainly in my own clinic, I can attest to people feeling and functioning better. We need, some better biological markers to track some of these things. We use clinical instruments that ask people how they're feeling or functioning, and certainly use things like the, UPDRS and so forth, but ultimately want these biological markers to confirm what we're seeing clinically. We talked a little bit about the design and outcome. I think of the, of the mouse studies. So has this then moved into human studies?

Noelle Patno, PhD: 27:28

Yes, there's a published pilot study with Parkinson's Disease. Patients for PS128. there, there are many other PS128 clinical studies, but just on the topic of neurodegeneration and particularly Parkinson's disease, PS128 was studied in Parkinson's disease patients and 68% of them reported that they noticed an improvement with the unified Parkinson's Disease Rating Scale. You mentioned the UPDRS. There were also improvements in motor scores, about a 10 to 15% improvement. And that was both in the on and the off state. And then based on the recordings and the diaries of the patients themselves, on and off states had improvements as well. Almost 48 to 50 minutes depending. And then what else? The PDQ 39 the Quality of Life questionnaire, which. a variety of domains activities of daily living, some stigma cognition, et cetera, that also showed improvement. So improvement in quality of life. Again, this was a pilot study, but very promising results.

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Dr. Ken Sharlin: 30:26

Are there some ongoing studies either that your company is directly sponsoring or that you're aware of outside of Bened Life?

Noelle Patno, PhD: 30:35

Yes, so Bened is working on designing future trials with PS128 Parkinson's Disease. We're also interested in talking to potential collaborators. Maybe we can talk a little after this call and explore, the best way to design that study and to recruit patients. Because even though Parkinson's disease one of the top neurogenerative conditions, it's still like 1% of the population, right? So sometimes recruitment can be an issue when, but when we have a, an isolated, when we have a clinic where that. The majority of patients are Parkinson's disease. It makes it a lot easier, then that can help us overcome recruitment challenges. And then we can also look for funding and also the proper design to make it a double-blind, randomized placebo controlled trial.

Dr. Ken Sharlin: 31:22

Yeah, absolutely. And fortunately clinics that are very accustomed to doing stool studies and things like that too would probably be helpful. Do think of. I often describe the gut and really our whole body, including the brain as an ecosystem and drugs of course important to the broad concept of what in general most drugs do. They have a targeted mechanism. We look for sort of a switch. We look for a pivot point that if we interfere with that one spot, if you will, then it has a downstream effect and perhaps all kinds of other things. But it's still a targeted treatment. And I'm wondering in, PS128 is of course, to a degree, a targeted treatment in the sense it's a specific isolated bacterium. But at the same time, when we introduce this. Exogenous bacterium into that microbiome, into that ecosystem. Are there influences on other microbes, and is it perhaps a synergistic effect? With PS128 and other microbes? Are you seeing other changes in that broader fingerprint that is the microbiome?

Noelle Patno, PhD: 32:37

So in some of the preclinical studies, like the ones I mentioned, they did see some changes in the gut microbiome. But then, a rodent microbiome is not the same as a human microbiome. There have been limited human microbiome samples in some of the clinical studies. The Parkinson's disease study did not look at the microbiome in particular. Interestingly, that population was also not constipated, though you might seek quite a few constipated Parkinson's disease patients. I think. In order to really interrogate that question about synergy, we'd need to really evaluate, okay. Look at the gut microbiome profiles, obviously. But we also, I think some of what I think is missing in some of these gut microbiome studies that I've seen is really controlling for the time of day. That's hard to do because people are not necessarily going to produce stool at the same time day. And I remember when I worked in a lab with in my PhD studies, there were people working on the circadian rhythm, how that affected the gut microbiome. So I hadn't seen that translate yet to a lot of gut microbiome studies later. So that's an open question in my mind. If you have circadian rhythms affecting gut microbiome, you have diet affecting gut microbiome, how do you remove all of these confounders and then look at synergy. You could look at in vitro studies, for example you could take gut microbiome samples from people. Create an in vitro model, add PS128. Try to see if there's some synergies there. Or you could isolate microbes that you're interested in from bifidobacteria whatever genus you're interested in. And, and then look for whatever outcome or output you're looking at. So if you assay or if you put those microbes alongside certain cells that you're interested, if they interact with those cells and then look at certain metabolites or immune producing. Immune molecules, cytokines, whatever then you could probably tease that apart a little bit. I think it depends on which of those questions do you wanna ask and how do you wanna do that? I know other scientists have looked at, okay, what about what's the right diet or food to take alongside a probiotic?

Dr. Ken Sharlin: 34:50

I took the question outta my mouth. I was almost ready to ask that. And even wondering, and, in that 12 week study design, whether there were any parameters for the subjects involved to stick with a similar diet or a diet at least at a certain amount of soluble or insoluble fiber or if a post hoc analysis did a breakdown of the different. If we could pull all the people in the study and kind of get a handle on what kind of diet they had, and then stratify them or put them in groups and then say, the people had the lower carb higher fiber is carbohydrate in a sense, but the lower refined carbohydrates, higher fiber, higher fat, or protein, whatever, how that maybe influenced the outcome of this study in those subgroups.

Noelle Patno, PhD: 35:38

Yeah, those are all great questions. It was a pilot study that wasn't designed with that analysis in mind. So a future study, it would be great to ask those questions. Give them, like a 24 hour dietary food recall, because that's one of. One of the better kind of ways to assess food intake and do that at various points and then, try to correlate that with, maybe their microbiome samples or their results from the PS128 ingestion. Those are great questions.

Dr. Ken Sharlin: 36:07

Yeah. And it's probably here we're talking on the podcast and we could have this conversation afterwards, but I'm gonna put it out there because I certainly, the recall type of approach is a, is very much a standard. We're involved now in to a degree and really starting our journey in remote therapeutic monitoring. Partnering with a company called Heads Up Health, that has created this dashboard like software it has a AI backbone, but basically it pulls data from a variety of smart devices, whether they're more in the health arena, meaning. Apple watches and Ora rings can't really make medical claims, but there are other devices out there that are approved for specific medical purposes. That can equally be monitored. And I know that while it may not be all that precise, there are apps that, let me just say I, I'm a foodie, but I don't particularly like tracking my food. I think it's very cumbersome to say, quarter cup of this and a half cup of that or whatever.

Noelle Patno, PhD: 37:13

Yes.

Dr. Ken Sharlin: 37:14

but now you can use your phone and take a picture of what you're actually eating. And these AI tools will analyze that food and approximate not only like proportions and macros and calories, but even apps like chronometer can look at micronutrient balance. And then it gives a more prospective rather than retrospective way to look at food and its relationship. To like PS128 and what it might be doing in Parkinson's or other disorders.

Noelle Patno, PhD: 37:49

Definitely when you have the technology, that's a whole new level to break out of the limitations of just questionnaires. And it's, it makes it easier on, on people, right? To just take a picture instead of think, okay. Was that approximately a quarter cup or what,

Dr. Ken Sharlin: 38:03

Yeah.

Noelle Patno, PhD: 38:03

say I agree. It's cumbersome to try to it or determine it yourself or put that little food scale right next to your plate at the table. so using the advancements in technology and having the funding to support that in a study would definitely advance the research in that area for sure.

Dr. Ken Sharlin: 38:20

Wonderful. So let's segue into Psychobiotics, and that's an area that your company has been very interested in, directly involved and really marketing this concept of psychobiotics mental health. And PS128. Can you talk a little bit more about Psychobiotics and Bened Life's and trend into that field and PS128.

Noelle Patno, PhD: 38:45

Sure. So Psychobiotics was defined. In the research literature over a decade ago by scientists calling it basically live microbes, that adequate amounts would confer a health benefit in psychiatric disease. So think about it as probiotics for mental or neurological benefits, right? A specific subcategory. Probiotics, it has also been loosely used to maybe include other biotics, maybe not just probiotics, so prebiotics or postbiotics as psychobiotics. I've told you about PS128 as one of the main psychobiotics. It's been studied, like I said, to support, balance dopamine and serotonin in the brain, in, in the preclinical models in Parkinson's disease, but also in early life stress model, which is a depression model. PS128 has been studied in multiple conditions, not just Parkinson's disease, but also four times in autism. So like the most clinically studied strain in autism, I would say. three of those were double I placebo controlled trials. It's also been studied, depression, it's been studied, Tourette syndrome, re syndrome. Also has other strains and some of them that have been studied as psychobiotics as well L-P-K-C-I PS23, which has been studied also in stress and in, it's being studied in math, cognitive impairment, I believe. And then so Alzheimer's disease, is of course an area of interest. We don't have a clinical study ongoing there yet, but the whole neurological area of mental health space would be open for advancements in psychobiotic research with PS128, PS23 PS150. And there are other probiotics in the pipeline as well.

Dr. Ken Sharlin: 40:27

And are some of these being commercialized into your products available for the consumer at this point?

Noelle Patno, PhD: 40:32

Yes. So the heat treated version of L. paracasei PS23 of HT-PS23, as we call it, has been combined with a lower. Level of PS128 a product on the market that we sell as well for stress because both of those have shown improvements in stress. And then also there, there can be a potential benefit in sleep. PS158 isn't ready for commercial primetime, but hopefully it will later down the line and. PS23 has shown benefits live, but we chose to, to launch the heat treated version because it's more stable. And it's also beneficial. So we could also launch like a live PS23 version. We could also look at the heat treated version of PS128 and see how beneficial that is as well. So those are some things to look out for.

Dr. Ken Sharlin: 41:25

Could you just tell me a little bit about this heat treated? And I'm not sure I understand that.

Noelle Patno, PhD: 41:31

Sure. So heat treated in a way that actually inactivates the live microbe. It's no longer alive, but that doesn't mean it's no longer active. This would be a post biotic. A post biotic is basically the inactive, inactivated microorganisms and or their components or metabolites that have health benefits when administered at adequate amounts. That's roughly the definition from the International Scientific Association, probiotics and prebiotics. So that's what I mean by the heat treated PS23 that it's heat killed. It's been heated so high that it's no longer alive. But either those cellular components, the metabolites or even the DNA itself be interacting with your intestinal cells or other microbes in the gut or your immune cells, and then having the beneficial effects later.

Dr. Ken Sharlin: 42:24

Do you think from a, just a very practical perspective, is it creating more shelf stable product as well? Does that play a role in some of the decisions to use that sort of thing?

Noelle Patno, PhD: 42:34

Yes, it's more shelf stable, so you don't have to worry about keeping it alive like refrigerating. Your average freeze dried, cryo protected microbes that are probiotics.

Dr. Ken Sharlin: 42:46

Nice. Very nice. We've talked a little bit about some of the different areas of human research that has been done. And I wonder if you're able to share what your company's current. Research pipeline looks like. What is the roadmap? What are you actually engaging and doing now and in the near future?

Noelle Patno, PhD: 43:06

Yes, so we have some studies with the newer mood combination, HT-PS23 and PS128 to further advance the research and the stress, mood and sleep benefits and potential GI benefits there. PS128 has been studied in autistic children. Really more of a three to 20, 25 age range. And we'd like to do a study in autistic adults primarily with the outcomes that are important to autistic adults. So that's where we'll need to first get the information from autistic adults themselves. What's of interest to you before designing that study. then, like I said, with heat treated PS128 with live PS23 with PS150 and some other strains in the pipeline. We're looking at research in Parkinson's disease research in Alzheimer's disease. There are other indications that aren't. Shareable at this time, but are also of interest. It's a longer list than you might expect but stress mood, anxiety, depression, those are also, in the mental health arena as well.

Dr. Ken Sharlin: 44:17

That's wonderful. Yeah. Just from a practical perspective, I'm I've never been involved in autism research, but we use that term autism spectrum and it just, in my experience as a clinician, when I'm seeing folks that have been labeled or diagnosed with autism, it really is a very wide, broad presentation. So I imagine you would have to more clearly define what you, who, what is the group that you want to study that is within that autism spectrum? They have to have certain types of behaviors perhaps, that are measurable, that then you can put within your protocol to determine if there are changes in behavior, changes in other things like sleep quality or learning or cognitive functioning, things that you wanna look at as a result, but it's a com. I imagine it's a very complicated area because there really isn't one sort of autism I suppose.

Noelle Patno, PhD: 45:17

Yes, that's absolutely right. So we are looking at a subgroup of non-speaking autistic individuals to the degree that we would need adults or ca caregivers or parents to actually out questionnaires. But then we could also potentially look at non-speaking. Spelling autistic individuals who are able to express themselves and communicate. Because one of the first, actually the first person to take PS128 was a non-speaking autistic adult who communicates through spelling and has been taking PS128 for over 10 years. So he's really opened the door for that group. It'd be great to do a study like on the, a larger group on that. And then, on the other end, autistic individuals who are a little bit more independent and they might be looking at maybe different outcomes related to reducing anxiety has been a typical theme. So it could be that, it could be GI health, whatever they tell us. But also, like you said, sleep. So we are looking at a more sleep deprived. Would you say a population of autistic people? Their sleep and that would be another category to look at.

Dr. Ken Sharlin: 46:23

I think one of the goals of having this podcast in the first place is really to share the larger toolbox with both clinicians and those affected or friends and family, of those affected, whether it's Parkinson's, Alzheimer's, ALS, MS, and so forth. And just show folks that there really are a lot of things out there that. Are available that they can do, that are science-based. And as I said in the beginning of the show, we value our pharma partners that we work with and utilize their products where appropriate. We want folks to know that is not the only solution potentially for them and they can do other things to take a major role in their own health journey. So within that in mind, if I was, we were talking to other clinicians how can we talk with them? What is your recommendation in terms of guidance on usage and expected benefits and even safety of introducing this line of probiotics into their clinical toolbox?

Noelle Patno, PhD: 47:28

So PS128 was studied at 60 billion CFU, so that's just. Only the dose that we recommend to practitioners when we're talking to practitioners. If you wanna use PS128 at the dose of the study for Parkinson's disease and autism, it's 60 billion CFU, and that's available in the neuralli and medical food which is intended for dietary management of Parkinson's disease and autism. And as a medical food, it's intended under the supervision of a physician or healthcare provider. In the Parkinson's disease study, it was interesting that it was reported to be taken in the evening. In the other studies, there wasn't necessarily a time of day, so we don't necessarily specify a time of day. It's more convenience. We do realize that it can be challenging for people sometimes to swallow capsules. And so these, you could take these capsules apart, open it and just put the powder in something that's cold. Not highly acidic and consume it immediately and should be able to go down and take it. There's a dog study, for example, where the the dogs had reduced anxiety and the owners used the opens, the capsules administered it however they needed to. And, the autistic children, the parents would have to mod, modify as well. Another thing that I think healthcare practitioners may ask is about. Using PS128 alongside other medications or therapies. Many of the studies, the PS128 was taken as a, like a nutritional add-on, right? So the Parkinson's disease patients were already on whatever L-DOPA they were on. it was unique to them. And then they took PS128 on top of that. The autism studies people had a variety of medications or therapies that they were doing based on their individual. Spectrum manifestation of autism. We don't necessarily have a record of all of the therapies or medications that were used, but that would then again, be under the supervision of the physician. From the clinical trials, it's also under supervision of a physician, obviously. There are some. Medications that we do know people took alongside PS128. So we could probably mention some of those. One of the main ADHD medications. I'm slipping my brain right now. But not that I think the methylphenidate, right? Yeah, the methylate that's, there we go. I remember now. So we don't know if it really has a strong interaction with. Drugs that could modulate serotonin or dopamine in the brain, but because it can balance serotonin, dopamine in the brain having that physician supervision there just in case somebody is sensitive, like we didn't study PS128 and serotonin syndrome, for example. So we don't know what would happen to people who might have that.

Dr. Ken Sharlin: 50:13

Yeah. Because of the nature of my clinic, and I really do see a wide variety of folks, but we have folks who come in from all over the world. Particularly interested in my more integrative, functional and regenerative medicine approach and sort of part of what I suppose the philosophy or value system that brings them to me is often folks want an approach that allows them to address their condition without the use of medication. And I really emphasize that. First of all, the use of medication should be very individualized but in the setting of Parkinson's. L-DOPA, as you've referred to many times, is really, it's just a dopamine precursor. It is what our bodies actually make. Our brain makes L-DOPA out of tyrosine and the carbidopa simply being that peripheral dopa decarboxylase inhibitor helps to ensure that the L-DOPA gets to the brain and doesn't get converted to dopamine, in the gut and then dopamine can't cross the blood-brain barrier. So we're no better off point being here for folks is that we're in no way discouraging folks from using L-DOPA. I always tell'em, it's if you were a Porsche or Maserati and it, the car was just parked in your garage and you're showing it off to your best friend and you're, and they're like, wow, that's really cool. Let's go for a ride. You say, I can't really do that'cause there's no gas in the engine. Like you need gas in the engine. That's your L-DOPA, that's your dopamine. So want folks to know that, of course, under the guidance of their physician and their personal care plan, that is a physician patient relationship. Or in no way suggesting that PS128 is simply a substitute for L-DOPA. And as you've said, even in the trials, these were adjunct. Therapies. But that being said, L-DOPA does have its drawbacks potentially. And the challenges of delivering L-DOPA to the brain in the most physiological manner is very much there. We've gone through different, clinical and scientific theories about when to initiate L-DOPA therapy? Back when I was a resident at at Vanderbilt University working with Tom Davis and that group, the, we were using a lot more dopamine agonists like Pramipexole because the thought was if we use L-DOPA. Too soon in the course of the disease that there was this neurotoxicity associated with it and that the, those who used it earlier were more likely to develop motor fluctuations than those who didn't. Or who delayed the use of L-DOPA. And now there have been at least a couple of studies that have refuted that and the dopamine agonists are less commonly used. We're back using L-DOPA earlier in the disease. But then we have companies like Amneal developing Rytary and Creon that are. Designed to deliver more physiological exposures, if you will, of L-DOPA in the brain, a more continuous exposure. So we're learning a lot more about, and we always have studied things like dopamine receptors and receptor density and sensitivity. Ultimately what I'm saying here in regard to PS128 is, combining your probiotic your neuralli neuralli from Bened life with your treatment for Parkinson's will probably more likely give you the best combination. The best boost and perhaps even as it synergistically affects dopamine release and perhaps in turn receptor density and sensitivity that you're ultimately able to provide a more physiological and robust application of these principles to the treatment of Parkinson's, and then we hope have better outcomes than drug alone. Any other just circling back around, we essentially we were talking about a targeted probiotic that is not inherently native to the human gut, but has pharmacological activity in effect through multiple mechanisms of action. But just finishing our interview with talking about gut brain health. As a scientist and expert in the field and just and a survivor of colon cancer who's successfully put her cancer into remission and ultimately can hopefully happily say, I don't have cancer anymore at all. Anything that you can share with our listeners or viewers about taking care of their gut?

Noelle Patno, PhD: 54:43

That's such a huge question always that people ask me, oh, how can you take care? How do I take care of my gut? Which product should I take? We start with diet, right? You go through this in your book as well. There are, you have great, lots of great recipes. I wanted to ask you what your favorite is taking care of your gut you've gotta have that foundation, right? You talked about gas in the tank, that foundation, that diet. I've seen a lot of Mediterranean diet. I've seen the mind, like the DASH and Mediterranean diet. For your foundation, and then you might have to individualize any vitamin or mineral supplementation based on deficiencies. Like a vitamin D deficiency, for example. That's I know from my personal experience. Omega-3 is typically something we supplement with. And then probiotics, like targeted ones for specific outcomes. PS128 has been studied, like we said, in these conditions like Parkinson's disease and then. You would need to look at other individual things that you might need. You also talk about magnesium in, in your book. I agree with that one as well. There, there are many things you need to individualize for your gut health. Obviously the pillars of health, of not just diet, but we've got our exercise, we've got our sleep, got our social connections having. Those social connections is so important also because we know that, lonely people or people with social connections and more stress actually have worse health outcomes as well. So let's not forget that holistic approach when we are considering a probiotic like PS128 or any other kind of intervention that we wanna do to support our gut and our gut brain health.

Dr. Ken Sharlin: 56:25

Wonderful. That's such an important take home message for folks. There's no magic pill out there. But that being said, there's some fantastic tools we can add to the toolbox. But build your toolbox around the foundations of sleep, nutrition movement, that mind body resilience and connection to others. Dr. Noelle Patno, PhD, chief Science Officer of Bened Life and really pioneer in the gut brain connection and the role of targeted probiotics. PS128 could play in. Can play in Parkinson's and potentially in other disorders affecting the brain like Alzheimer's and autism and depression.

COMMERCIAL BREAK: 57:14

Hi everyone. Dr. Ken Sharlin here with the Healthy Brain Toolbox. I'd love to hear from you. If you have general questions about brain health, neurology, or the science of keeping your brain sharp. Send them to questions@healthybraintoolbox.com. I'll be reading your questions on the upcoming episodes. Please remember, these need to be general questions, can't answer personal medical questions, or provide individual medical advice. So if you've ever wondered about brain health strategies, lifestyle tips, new research, or the future of neuroscience, send those questions in. I look forward to hearing from you and who knows? You might even hear your question featured on the show.

Dr. Ken Sharlin: 58:06

Thank you so much for being part of the Healthy Brain Toolbox today.

Noelle Patno, PhD: 58:09

Thank you again for having me, Dr. Sharlin, it's been such a pleasure.

outro: 58:12

Thank you for tuning into the Healthy Brain Toolbox podcast. I hope today's conversation gave you new insights to protect and nourish your brain. Be sure to subscribe, leave a review and share this episode with anyone looking to take control of their health. Until next time, stay sharp and keep learning.