Transcript

Derek Smith:

Hello and welcome to Baylor Connections, a conversation series with the people shaping our future. Each week, we go in depth with Baylor leaders, professors and more, discussing important topics in higher education, research and student life. I'm Derek Smith and our guest today is Dr. Joaquin Lugo. Dr. Lugo serves as associate professor of psychology and neuroscience at Baylor, a leading researcher into autism spectrum disorder. Dr. Lugo studies, the relationship between epilepsy and autism and other genetic conditions. CDC estimates say that one in 54, American children meets autism spectrum disorder criteria, highlighting the need for work such as Lugo's. A Baylor graduate, he returned to his alma mater in 2010 and established the Lugo Lab, where he's earned nearly $1 million in recent funding from the National Institutes of Health to support his work. Well, certainly autism is a topic we hear about in the news. Probably everyone knows a family, if they don't have a family member themselves, who deals with this. And so we're excited to talk with you about this today, Dr. Lugo. Thanks so much for joining us. It's great to have you here on the program.

Joaquin Lugo:

Oh, you're welcome. Yeah. Thank you for inviting me.

Derek Smith:

Great to visit with you and let's dive in by, just curious what drew you into autism research? When we think about psychology and neuroscience, there's a lot of different ways you could go. What drew you into this area?

Joaquin Lugo:

Yeah, so I was thinking about that. I think it's always my larger interest has been looking at trying to understand how the developing brain works. And what I was really drawn to is seeing how insults can impact the developing brain. And even when I was in graduate school, I was investigating fetal alcohol syndrome. And during that time I was looking at how insults such as alcohol could impact the developing brain. In particular, how it impacts social behavior and those kind of autistic like behavioral deficits. And then as a post-doc I then continued on in epilepsy, but still with that kind of interest, more looking at development and how these insults can result in these autistic like behavioral deficits. And just across numerous investigations, one thing I found is that changes in social behavior and communication just seemed to frequently happen. And as I started to know more from families and looking at how odd autism impacts people on a more global sense, trying to understand what they're confronting and also just what are the mechanisms that may underlie autism. And then what I can do to provide treatment.

Derek Smith:

Visiting with Dr. Joaquin Lugo and Dr. Lugo, autism is a term that we hear about a lot. As we mentioned, CDC estimates say one in 54 American children meet criteria and it's something that, because there's a lot we have yet to know, can spread a lot of maybe misinformation in some cases or just misunderstanding in others. As we work towards sort of a common definition about what we're talking about for the next 20 minutes or so and hopefully for people who are interested in this topic beyond that. When we talk about autism spectrum disorder, what specifically are we talking about?

Joaquin Lugo:

Okay. That's one area because it is now a spectrum so it really encompasses a lot, but what I'm kind of focusing in on more and what a lot of the work that we're talking about today will be really in, children have this particular challenge in communication and social behavior and who also may show these aberrant repetitive kind of behaviors. And so those three are the really the core that are really kind of used to diagnosed autism.

Derek Smith:

What aspects of autism spectrum disorder make it challenging for anyone seeking to find a treatment, whether that be researchers like yourself or parents with a child who has ASD?

Joaquin Lugo:

Yeah, I think that's been one of the biggest difficulties in the field. And so for one, there is no diagnostic test. You can't go to the doctor and get a blood test or even a genetic test and say, "Oh, my child has autism." And so what you have to rely on is the doctor observe the behavior of the child and then making the diagnosis. Now it is possible that she could make the diagnosis about 18 months of age, but some estimates I've found, could be up to more like four years of age, where they feel pretty confident that that's the diagnosis of autism. And then during the time, the parents were just wondering what's going on? And how do we understand how this works? And so that does create a lot of challenge. In addition, since I do a lot of behavioral testing in my lab, even with some mice, is that whenever you do behavioral tests and there's no real clear standardized way to perform this particular behavior or observe this particular behavior. And so you have a wide range of diagnosis in the fields and across numerous different physicians or psychologists and even one criteria can be where they are very interested in people, but they don't really know how to talk, to play or relate to them. And that's something when you see that kind of diagnosis or that kind of measurement you go, well, how do you really know that? And so that's where the huge challenge is just, it's so difficult to have it be a really clear cut diagnosis for this. And then with that, it creates a lot of variability across this. And so it could be that the child has autism, but perhaps that there's a treatment out there for certain aspects of autism. And so a parent may hear, "Oh, there's this treatment for autism," but it's like, well, it's for this particular kind of autism or this particular behavior in autism. And so that's what one of the challenges of variability is, is that there is many different groups and you can't always pull from one area to the other, even though it does fall under the umbrella of autism, there's many different subcategories that it's hard to really understand, even if there are treatments available, who's going to best benefit from those? And then just trying to compare one group from the other may not be as clear cut as we would like it to be. It just makes it really a challenge for those who are studying it as long with the parents who are just trying to understand what my kid's autism, but then not knowing that there's many different categories. And you really have to think about the group being investigated because it can be really quite different than what you're dealing with as a parent.

Derek Smith:

From a scientific perspective, are there things that you would say that you and your fellow researchers and scientists do have a grasp on when it comes to this? Just in terms of, are there a few things that you can say, "This we know?"

Joaquin Lugo:

I think one thing that's been, there has been a lot of progress in, is that there's a pretty large or a pretty significant understanding of the role of genetics in autism. That's been one area that there's been a lot of funding and a lot of interest in is to try to understand, what are the mutations or what are the genetics that are involved with autism? And in many cases it's not one particular mutation, but several of them, but that's one area in the last 10 years, it's really grown in terms of trying to understand that. Along with that, just trying to investigate other factors that could lead to autism. One thing we know in the epilepsy field, now autism is that the use of valproic acid, which is used as an anti-convulsant, that's used during pregnancy, does really lead to a huge increase in children having autism with it. And other settings could be things such as it's a higher likelihood for a child to be autistic if they're born to a father who is much older. And so I think we're really understanding a lot of the genetics and the factors that increase the likelihood of the child having autism. And then really in the last probably 10 years or so, there's been a huge push towards treatment to try to understand, what are the different contributors that we can use for those with certain aspects within autism. And there's been a huge push by different organizations, parent advocacy groups and stuff like that for their child. And to really look for less of just trying to understand the cause of it, but what we can do to treat them. And so that's been something that's really grown quite a bit the last couple of years.

Derek Smith:

You talk about families and a lot of them have been real champions for their children. A little later on in the program I want to ask you about places where they can go to find information, information that's scientifically vetted. We'll be asking you about that a little bit later on in the program so if families are interested, know that we'll talk about that a little bit later, as we visit with Dr. Joaquin Lugo, associate professor of psychology and neuroscience here at Baylor and a leading researcher into autism spectrum disorder. I gave an overview of your research, a very brief descriptor of it. Could you take us a little bit more inside your areas of focus and the way that you approach going about seeking a understanding or discoveries.

Joaquin Lugo:

Okay. For my area, since I've researched autism, but also epilepsy is that some years ago, others have found that there's a high relationship between epilepsy and autism. And so for those who have autism, about a quarter of them, you see that they have epilepsy or some sort of abnormal epileptiform activity and then inversely about a quarter of those with epilepsy also have autism. And so my particular area has been trying to understand that relationship there. What is the relationship between autism and epilepsy? In the hopes that we can have better treatments for those with autism, as well as those with epilepsy, by looking at this particular relationship between the two. And what I've then done is then look at how seizures impact the brain during early development. And then look at a number of different intracellular signaling pathway changes and also alterations in neuro-inflammation during this period here that then lead to later deficits in communication, social behavior and other autistic like behavioral deficits. And so that's kind of the main area that I look at is just inducing seizure then seeing how that can lead to autism and then really diving into those neuro-mechanisms that can help us to provide new insights into that relationship.

Derek Smith:

We're obviously kind of going inside the brain here a little bit. Can you help us a picture a little bit better when you talk about things like pathway changes and the impact, you mentioned insults at the top of the show, little insults that maybe they happen many times that can add up. Can you help us kind of understand a little bit more what those things mean and what they look like?

Joaquin Lugo:

I guess what they mean is, after this insult and it's very normal for the brain to have some sort of response to this and sort of homeostatic response, but what happens is it becomes prolonged and now it becomes aberrant. You may find a change in different ways in which the cells or within the molecules within the cells are communicating with each other, but now they're hyperactive. And so now they're functioning in a level that's too high or too low. And with that sustained over a long time, it really changes the properties of those cells in the brain, which then later on could lead to the individual becoming epileptic if there's this push towards more excitability. And along with that and this kind of goes into the idea of one theory of autism is that there's still very much this theory that a lot of what we're looking at is sort of the synaptic theory of autism is that many of the modifications that are occurring seem to be altering the synapse. And when you alter the sensor cross in millions of neurons, that's when you see this aberrant communication and could be why this aberrant communication could be why there's difficulty in processing communication or social behavior, things that are pretty complicated to really put together and you see how the disruption in the synapse across millions of neurons, how that could lead to the individual having difficulty in performing those kinds of behaviors. And so a lot of our work is really trying to gear towards how these changes are changing the synapse and how that could lead to these behavioral outcomes.

Derek Smith:

Visiting with Dr. Joaquin Lugo, associate professor of psychology and neuroscience at Baylor today, here on Baylor Connections. And Dr. Lugo, you mentioned neuro-inflammation a few moments ago and I know that's one area you've studied as of late. Could you tell us a little bit more about that and maybe what aspects of neuro-inflammation drew your attention in research?

Joaquin Lugo:

Okay. This is an area that quite honestly, I tried for a very long time to not get into just because the brain by itself is really quite complex and you start adding in inflammation, there's just many, many variables to look at. But one thing I and many others kept finding is that there were just many changes in inflammation. For instance, we use this one, it's a monogenic model of autism. It's called the fragile X syndrome. It's a mouse model with mutation in this particular gene that mimics fragile X syndrome and we found in this mouse is they have a different baseline level of neuro-inflammation in particular parts of the brain. Thought, aha, that's kind of interesting that it just at the base level, they seem to have different properties of inflammation that are different from their wild type or the ones that don't have this mutation. And then second, when we challenge them, we give them something it's called a lipopolysaccharide and what this is, is the outer membrane of a gram negative bacteria and it's a very good kind of experimental way to induce inflammation. And so in our mouse that have the mutation for this gene that's responsible for fragile X syndrome, there, even though at baseline they're lower, actually here, they have a higher response. And so they have an inflammatory response to this particular toxin. And so with this and then looking at other measurements too, we find after seizures, you see this increase in inflammation. It was just something we just keep finding this change again and again and again. And luckily there has been a lot of interest in this area from other areas of neuroscience. And so there's now lots of therapeutics coming out. And so timing wise, if it was a really good time to go, we see this change in neuro-inflammation. There seemed to be all these therapeutics coming out for other neurological disorders, this could be a way of kind of tying that into this area and seeing if there's been maybe a new treatment for epilepsy and autism.

Derek Smith:

Talking with Dr. Joaquin Lugo. And Dr. Lugo, you mentioned that this is an area that you initially had resisted going into talking about some of the complexity. I'm curious when you think about how should we picture all of the variabilities that go into the way the brain and eventually the body responds to different, whether it be insults or different inputs. It seems like when, just hearing you talk, that when you think about kind of the if then aspect of if this is present, then this, but then you start adding multiple variables. And it seems like it can get very complex very quickly. How should we envision that, especially as it relates to the work that you and so many researchers are doing?

Joaquin Lugo:

Well, I think for one, we can kind of get hung up on, a particular measurement. I may look at, just call it cytokines and kind of pick a couple of them. But I think one, if you keep it a bit more generally, as just saying, there's a change in neuro-inflammation and there are some more global ways of suppressing it. And so, even though we like to get into the mechanism of this occurring with this, this, and this, sometimes just things that kind of generally suppress may have overall in some ways simpler outcomes. And so many of us really kind of go into the weeds and try to understand how that works. But I think from those on the outside, be focused less on that and be focused more on, what is a general treatment trying to do? And it can be that we don't necessarily know all the specifics about how it's occurring, but that the overall outcome is in some ways simpler than all the different components with it. It can get very easily complicated. But I think when you kind of pull back a little bit, many times the treatments that we're trying to induce are very global. It's going to be, suppress this one pathway or increase this one here. And I think that's easy to understand and easier to kind of to turn to get an idea of what researchers are trying to do.

Derek Smith:

Visiting with Dr. Joaquin Lugo and Dr. Lugo, let's zoom out a bit, we talked a little earlier about families. We talked about the fact it can be a real challenge to get good information and there's a lot of rumor out there. And sometimes those rumors can get a prominent placing, as in social media or the news or what have you. How would you recommend families vet sources, approach information that they might hear or see online so that they can feel as confident as they can about what it is that they're thinking about in terms of the child they want to help?

Joaquin Lugo:

That's a great question. I think because there's so much behavioral emphasis in the field, it's pretty easy to manipulate either knowingly or unknowingly from those we're trying to help, but perhaps leading people the wrong way. I think for one and this is just in general, any kind of group or therapy that claims to be the answer and will fix all, is going to be incorrect. If that was the case, we would have found that out a long time ago. And I can see this in preparation for this, I was looking back on some different websites and it's some of the therapies have been out are actually quite dangerous and there've been ones using bleach for autism, using chelation therapy, all kinds of things. Of course, the big anti-vax movements really has its roots in trying to prevent autism. And so there's been a lot of really terrible information out there, but I think for one in general, anything that's a cure all for it, is just something to just really avoid because there's just no such thing for anything really. And I think, beyond that, look at organizations that are affiliated with scientific societies. And so one is the International Society for Autism Research or InSAR is one. There's Autism Speaks, Frexa. I think those who have an affiliation with scientific societies, with universities, are much more in tune with what's occurring in the field. And where do you go from there? One could be talking to developmental pediatricians or child neurologists or child psychologists, those in the field that can kind of gear you to good, reliable source of information. If you look at any of the big universities, the big medical centers, you can then kind of look through there and see where they will say, well are these are some affiliations with different advocacy groups, are ways to go. Doing a blind kind of Google search can lead you to really some pretty terrible kind of areas. But I think on the front end, really putting some time and seeing if it's reputable and by seeing the science based, those are really good ways to go for what's kind of current in the field and what's going to lead to really better information for them. Because like I said, there's just so much terrible information out there and you really need to be really careful a consumer of this information because you can be led to some pretty dangerous areas. Some of these therapists they have out there are really quite dangerous and the therapists themselves could be much worse than the problem that they're currently dealing with. But those are some the areas I would look into that could be positive ones that any kind of university based or any affiliation with scientific societies.

Derek Smith:

Good thoughts as we visit with Dr. Joaquin Lugo and Dr. Lugo, as we wind down, I'm curious as we look towards the new year 2021, what's ahead for you and your work? Are there any aspects that you're very most excited or intrigued to pursue in the coming year?

Joaquin Lugo:

Yeah, so there's a couple of different things we're doing. For one, I have a grant going out in the next couple of months where really trying to investigate how by inhibiting inflammation, and I didn't go into the insula signaling pathway, but this particular pathway and also use different dual therapies. How have we can do that during early development with those who have seizures, how that could potentially protect them and where they won't have these later autistic like behavioral deficits. And so trying to use some of our therapies during early development to do that. Beyond that, one thing we've done, we're hopefully going to publish the next couple of months is looking at vitamin D. It's a high fortified vitamin D diet and how that could help to restore some autistic like behavioral deficits in this a different mouse model that we have for autism. And really in general, that's one thing I think we're finding more interest in doing is looking at the role of what are some different dietary manipulations that we can perform that can be used as therapeutics, because those are much more likely to be applicable or useful for the general public than it is to inject your child with some sort of therapy. That's probably not going to be the way to go, but looking at how we can manipulate diet in different ways to see how those can be therapeutic. I think some areas that we're getting some momentum with and seems to be quite promising and also then hopefully very useful to those who are trying to find therapies to help with their child.

Derek Smith:

That's great. We'll look forward to hearing more about that. You'll have to keep us informed as you learn more. Well, we really appreciate your time on the program today. Thanks so much for the work you do and thanks for joining us here on Baylor Connections today.

Joaquin Lugo:

Yeah, you're welcome.

Derek Smith:

Thank you, Dr. Joaquin Lugo, associate professor of psychology and neuroscience at Baylor, our guest today here on Baylor Connections. I'm Derek Smith. Thank you for joining us. Want to remind you that you can hear this and other programs online at baylor.edu/connections and you can subscribe and leave reviews on iTunes. Thanks for joining us here on Baylor Connections.