About this Podcast
What’s the state of clinical trials in autism and neurodevelopmental disorders? What’s on the horizon?
Scott J. Hunter, PhD, a member of WCG’s Scientific Leadership Team, shared his insights during a recent conversation with Mark Opler, MD, PhD, Chief Research Officer at WCG-MedAvante-ProPhase. Dr. Hunter is a professor of psychiatry and behavioral neuroscience, as well as pediatrics, at the University of Chicago.
The interview has been edited for clarity and length.
Dr. Opler: Can you give us an update on the overall state of the field in clinical trials in autism and neurodevelopmental disorders. What’s new and exciting?
Dr. Hunter: One of the most exciting things that I've been involved with is the identification of the risk and the range of severity of autism spectrum disorders and other neurodevelopmental challenges in children who have been born prematurely and at very low birth weight.
As a result of this ongoing research, we have a better understanding of the risk that exists for these individuals. In the past, they were very difficult to manage; now, with many changes in neonatal care, they are showing much greater advancements in their development.
In this population, it’s important to understand the risk for a range of challenges that are consistent with the identification of autism spectrum disorders and how to best look at ways of treating them, given that in many cases, autism spectrum disorder is actually more tied to a higher functional profile, one where there is greater prevalence of co-occurring ADHD. We’re seeing more work and greater understanding in this area.
What I've been most intrigued by is that we are beginning to better understand the broad range of phenotypic differences that contribute to making sense of what we classify as the autism spectrum disorders. We’re developing a better understanding of the different variables at play that predict risk, which then allows us to begin to better identify groups where different treatment approaches and different compounds may be the most useful.
Dr. Opler: There's renewed interest in the gut and the GI microbiome as a potential target. Can you give us any insights?
Dr. Hunter: I think one of the things that’s been very intriguing to me has been the growing investigation with individuals who are vulnerable to developing symptoms consistent with autism spectrum disorder and the relationship with the environmental factors; looking at the microbiome is giving us a new window into this.
Looking at the relationship between the environmental factors that may be at play prenatally and postnatally may give us a greater understanding of segregating different phenotypic expressions. I think we’re already beginning to see some of that play out.
Dr. Opler: Let’s move from the gut into symptomatology. There’s been a lot of focus on agitation and aggression and a certain amount of focus on attention. Are we finally moving beyond those domains? Are we getting to what some of us think are more core, such as the social impairments and impairments in social cognition and performance? Are there any signs of progress that merit discussion?
Dr. Hunter: Without a doubt, there are some indications coming from a series of different drug trials. We can begin now to focus much more directly on the social and the reciprocal communication considerations that are at play. We have a better understanding that one of the key features across autism spectrum disorders is this barrier to effectively make sense of information typically transmitted socially and through the face. There’s now a much greater emphasis on efforts to try to guide more effective interactions, and to do that from an earlier stage of development.
This means identifying individuals at later infancy and very early toddlerhood to begin intensive work on the behavioral side. But we’re also beginning to look at whether the compounds that address the anxiety and inattention features could support and better guide our ability to then address those social concerns.
I also am aware of the goal to better understand some of the neurochemical considerations that underlie social processing, looking at particular hormonal- and neurotransmitter-based for compound research.
Dr. Opler: Obviously Balovaptan has received considerable attention. This is a small molecule acting as a vasopressin receptor. It received breakthrough designation by the FDA early last year and has moved into phase three trials. Do you have any thoughts about Balovaptan to share?
Dr. Hunter: I find this very exciting research. To be upfront, I’m involved with colleagues who are co-PIs on the Balovaptan studies. We’re now looking at late adolescence to young adulthood, focusing on individuals whose social challenges are of most concern. Given the research that’s been done already with this compound, this is a really promising area, and it’s an exciting one. I’m involved in helping do assessments for subjects in these studies, so it’s giving me a chance to get in on the ground floor and see what exactly is being focused on. And the key with this is really looking at adaptive social functioning, and research to date has been very promising.
We’re at a stage now where we are able address multiple challenges that are at play for individuals with autism spectrum disorder; that puts us in a very different place than we were even just 10 years ago.
Dr. Opler: Do you have any news about the assessment of autism? For many years we’ve had the same measures, the same batteries.
Dr. Hunter: That’s a tougher one because right now I would say, specifically from the psychology realm, the emphasis continues to be on utilization of the Autism Diagnostic Observation Schedule. The decision to utilize the M-CHAT and other measures developed with pediatricians and with developmental clinicians, very early on, is important.
Several studies are now looking at both refining measures like the M-CHAT as well as measures that allow us to more effectively address certain behaviors and concerns like the autism diagnostic schedule and a number of other tools that have been traditionally less commonly used. One of the challenges has been having measures available that can be used in clinical trials and to gain the information in an effective way. And I think that’s an area that’s beginning to be refined.
Many of these measures are now being translated in other languages. I’m particularly interested in the movement to use the ADOS, the M-CHAT, the social responsiveness scale and SEQ in China.
Dr. Opler: I think one of the things that intrigues a lot of people in the area is the potential for moving beyond traditional scales and into technology. Is there a role, for example, for wearables? Is there a role for more automated methods of analysis that will help us transcend some of the challenges we’ve historically faced? Is there a role for technology as an outcome measure in treatment studies and intervention studies?
Dr. Hunter: Without a doubt. I think the research, looking at eye tracking, and that we now have methods for using eye tracking technologies in diagnostic settings, is something that is under investigation and is moving forward. The other interesting thing is the use of virtual reality as a component of assessment. Putting individuals into situations where they actually have to demonstrate live how they’re able to engage is proving to be very useful.
One of the things we have found about individuals with autism spectrum disorders is that they often are more comfortable engaging with technology. So not only do we see areas of challenge for them, but we also can use these tools. And at least in the empirical settings, they have been shown to be very helpful in understanding greater strengths that individuals actually have that we’re not necessarily able to pick up in a one-on-one social interaction, human to human.
Dr. Opler: How long will it be until these kinds of measures are ready for prime time? Whether it be in drug trials or other forms of intervention research?
Dr. Hunter: I'm going to be optimistic here: I think within five-10 years we’re actually going to see a much greater opportunity for using technologically based assessment tools. One of the things that’s taking place right now that’s a little bit of a challenge, in terms of making the adjustment, is that most of the traditional measures for looking at cognition and looking at a number of the various psychological functions are moving to technological models as opposed to traditional, interactive, pencil-and- paper types of model assessments.
And I do believe that with challenges in the neurodevelopmental area–including autism spectrum disorders and some of the intellectual disability syndromes–we're finding that we can gain more information by moving to iPad-based presentations and using more computer-based systems. And I think that really, by 10 years from now, they're going to be in a whole new world with doing assessment. I think that will allow us to do far more real-time consideration and actual consideration within the environments that the people interact in on a day-to-day basis.
Dr. Opler: Now, let's shorten our horizon a little bit: What do we have to look forward to in, say, the next year or two that you think is going to be exciting for clinical research and for treatment of folks with autism spectrum?
Dr. Hunter: Well I think, without a doubt, within the next two years, we’re going to have some very intriguing data from a number of ongoing studies, many supported through the NIH and through the ECHO Consortium. Looking at biomarkers that help us better understand the relationship between the environment and risk by both looking at information regarding the microbiome but also even more directly at neurofunction, in tandem with looking at a series of different serums and other biomarkers.
I also think that within the next two years, we’re going to have a really good understanding about the usefulness of the compounds that have to do with addressing social functioning and how we can take advantage of those in conjunction with more active and assertive behavior interventions, and start to do some pretty interesting real-time investigations.