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Welcome to SCN2A Insights, bringing you the latest research and clinical updates on SCN2A and genetic epilepsy from around the world.

Dr. David Cunnington: So welcome to this episode of SCN2A Insights, and welcome again, Kris.

Kris Pierce: Thank you.

Dr. David Cunnington: So in this episode, we will follow up with our prior episode, where we interviewed John Spiro from the Simons Foundation. And who are we talking to in this episode, Kris?

Kris Pierce: In this episode, we speak to Jennifer Tjernagel, who has been at Simons for many years, and is across many of the programs that they run, including the SCN2A Registry.

Dr. David Cunnington: So thanks a lot, Jennifer, for joining us on the podcast.

Jennifer Tjernagel: Oh, my pleasure. I’m glad to be able to talk to you.

Kris Pierce: So Jennifer, can you just introduce yourself, what your role is at Simons, and also highlight how long you’ve been there?

Jennifer Tjernagel: I am the Senior Project Manager for Simons Searchlight, which was formerly known as Simons VIP for many years as well. My primary role is sort of to shepherd all of the research activities from inception to completion, make sure that working with our team on lots of the logistics, and overall supportive role.

I started with the foundation in 2010, specifically on Simons VIP. And so that’s gone through the initial phase of much more of an in-person multi-day assessment type study, where participants were having to go into clinical centers. And now, a much broader scope of the online registry model.

Kris Pierce: What is Simons Searchlight mission?

Jennifer Tjernagel: Yeah, so it might be helpful, I’ll give you a little bit of background of how we started with Simons VIP/Simons Searchlight, and why we started. Because I think that really informs the mission of where we are today.

So back in 2010, when we started, we had been involved in a previous cohort called the Simons Simplex Collection, which was collecting individual’s data for families that had one child on the autism spectrum, and one child without, and looking into the genetics behind that.

So really doing a deep dive into the phenotype clinical presentation, but then at the same time doing genetic sequencing to see what was popping up as the most frequent genetic findings. So one of those findings that came out of the Simons Simplex Collection was 16p11.2 deletion and duplication syndrome.

So the idea was in taking the autism spectrum, which is extremely heterogeneous, and seeing if we were to look specifically at a particular genetic group within that, if we would be able to come to answers more clearly, and hopefully, looking at a more homogenous group of those individuals. So the original idea was to really take a genetics first approach to the research rather than starting with the clinical presentation from there.

Obviously, in the past many years since we started, there have been so many more genetic changes that have been associated with autism and other neurodevelopmental disorders. And so our list of genetic findings that we’ve been interested in studying has grown and grown, and grown.

And where we see our role in our mission currently is, is to continue to try to be a catalyst and to accelerate scientific progress into these genetic disorders, specifically, by trying to make things as easy as possible for researchers to access information that we’ve collected in a standardized high quality manner, as well as biospecimens we’ve also collected, and any other resources, and just the underpinning of having a structure there to collect information that’s important.

So really, it’s meant to be a supporting role and the overall– in line with the overall mission of the Simons Foundation, really just to speed research into these conditions, and be as open and transparent with all of this information to get it as to as many scientific minds as possible to get answers in the end for all the families.

Dr. David Cunnington: Although Kris and I’s specific interest is in SCN2A, how many genes is Simons Searchlight looking at?

Jennifer Tjernagel: Currently, we have quite a large list of genes. It’s close to 220 different genetic conditions. That being said, that is our list of genes that are eligible to join Simons Searchlight. And we have a group of highly engaged patient advocacy organizations that I would say is closer to 25 genes where we really have made some meaningful progress in recruiting individuals and collecting data from them.

But we fully expect that over time, the number of groups that we engage with is going to continue to fill out and grow exponentially.

Dr. David Cunnington: So having a registry is one of the functions that Simons Searchlight is doing for genes. Just describe for us a bit what’s involved in a registry, and for example, SCN2A Registry.

Jennifer Tjernagel: Yeah, that’s a great question. And I know that many groups are interested in starting a registry. And I think that you can look at a registry at many different levels. At the very basic level, it could be a registry of contact information for any given researcher.

At the other end of that spectrum, you could have a full-blown natural history study where you are collecting information online and also in person. The Simons Searchlight Registry really is a blend of that, and that it really aims to collect not only basic identification information and contact information for future research projects that come up that we can invite families to, but also a meaningful set of clinical medical history information, other standardized measures as much as possible to look into the behavioral components that individuals are experiencing as well as you know, basic demographic information.

We also have the capability of collecting all of the genetic, the clinical genetic reports, data and extracting information from those for researchers, as well as where families have access to medical records. We can upload those into our system, and we’re constantly looking for other avenues of other types of data we can collect.

I think the most important part of the registry is not just the baseline information, but knowing that we’re following individuals over time to really be able to answer the important questions for many families of “what is this,” “what is the trajectory look like for any given condition,” and “what can my family expect once we get the initial diagnosis?”

Dr. David Cunnington: And on that note, what does it look like for a family that wants to participate in the registry? You know, they’re interested, they want to sort of share their data. What’s that process look like and how do they go about it?

Jennifer Tjernagel: Yeah, we try to make it as easy as possible, and are always looking for feedback from families on how to do that. The way that any given family would currently participate in the research is everything is online, as far as signing up and registration. So they would go to the website, there’s a button that says Join Us.

And once they do that, they’re led through a series of screens that provide information about the project and the research behind it. There’s a consent form online that they’re able to read and sign. And then it leads them into the process of uploading their lab report. Mostly, that’s a very important component to make sure that when we share data with researchers, we can guarantee that they actually are getting, comparing apples to apples in terms of a genetic diagnosis.

Once they get through all of the basic registration information and upload their lab report, they can then go to their dashboard, where they will see different surveys that they can fill out. And then at the same time, they will be contacted by us to schedule a phone conversation with one of our genetic counselors who will talk to them over the phone to get a detailed medical history, which is very helpful because, we have a standard, several very talented genetic counselors that help us out. And they can have the opportunity to ask a lot of follow-up questions of families. And we find that that really increases the consistency of the data and the data quality, and how the medical history is reported.

So once they get done with all of their baseline surveys and medical history, participation can be their yearly follow-up. We have newsletters, we have webinar opportunities, and we also have the opportunity to participate in other studies that we hear about from external researchers that we can alert families to if they’re interested in even doing more.

Dr. David Cunnington: So the families completed that process, they’ve uploaded their data at the back end, then what happens? What does Simons Searchlight do once that data is then uploaded?

Jennifer Tjernagel: So we have a team of analysts that then will take the data, and review it. We have a set of data quality procedures that we go through. And then the data sets will be released to an area of the Simons Foundation platform called SFARI base. So it’s S-F-A-R-I base, Simons Foundation Autism Research Initiative is what the acronym stands for. And that is actually the portal by which researchers will go on to apply to access the data and the biospecimens.

And once they get approved, they can download those and order their samples. One thing that we do ask is, as part of the agreement is that any new data that’s generated by the researcher, gets deposited back into the Simons Searchlight Repository, just so that, overall, the knowledge base can continue to grow.

Dr. David Cunnington: Yeah, that sounds like a really great collaborative type of relationship. So you’ve got the information to share but share information back the other way so that everybody benefits from it. That sounds great. If people are looking to collaborate with Simons Searchlight using some of the registry data, what’s it look like from a researcher point of view? What do they need to do?

Jennifer Tjernagel: One of the aspects that we really are looking forward to using frequently in Simons Searchlight is something called, Research Match. So that’s where when we look at collecting data across the various communities that we study in Simons Searchlight, one of the benefits of this whole enterprise is really being able to look across different genes that may be related in different ways, whether it’s a biological mechanism, some sort of other relationship between the genes and their function, their effects.

So it’s very important to us to have a consistent set of data that’s collected. Now, what we hope is by the researchers looking through that data, this will help percolate additional questions, areas that they want to do deep dives in, and say they want to have a very specific survey or other research opportunity specific to SCN2A. Then they would be able to access the Research Match component of the project where they could do something that’s very specific to that genetic disorder.

And then we, through our system would send that out to the SCN2A community to collect that data. The data then would become part of the Simons Searchlight Registry automatically, as well as being shared directly with the researcher.

So in terms of looking forward to collaborative opportunities, ideally, we would be able to see the researcher’s base knowledge of the condition and then also help facilitate them do future research projects with fewer barriers.

Dr. David Cunnington: Yeah, and there’s nice examples of that. And one of the SCN2A examples where were obvious, the natural history study that’s run out of Melbourne, but running globally, and the collaboration that they’re formed with Simons Searchlight in the way that’s going to add to each of those databases.

Jennifer Tjernagel: Yeah, I think it’s important for families, because it does take so much time and we recognize that it takes a lot of time to fill out this information and get on the phone with us. And if they’re working with multiple researchers, I think there’s a sense of need from the families to know that these different places are talking to each other and sharing information, and that it’s all going to be put together and the different pieces of the puzzle with lots of different people contributing.

Kris Pierce: So Jennifer, I just wanted to ask sort of circling back a little bit to access for families. You recently introduced Spanish, so other families can access, who don’t speak English, because your programs are global, and most of our rare groups are global, and there’s not many. So having as many families being able to access is important. What’s your aims with access for other families?

Jennifer Tjernagel: Yeah, we are so excited to have gotten to the point to launch our first language other than English. It’s something we’ve been wanting to do for a very long time, because we recognize that these conditions are so extremely rare that you really need the power of finding individuals all across the world to power the research and contribute. And that we definitely recognize that there’s also a desire from families all over the world to participate.

So we’ve chosen several initial languages, Spanish was the first to reach the starting gate there. But we already have three additional languages lined up to launch. And much of that is driven by the patient advocacy group organizations telling us where they see the need. You know, we have an engaged group in Germany that really wants to participate. Or, you know, we’ve obviously heard about groups in Spain and also in the Netherlands.

And so I think that it really helps when we’re partnering with families to know where the needs are, because we do want to engage. We found that the best way to do in recruitment is through family organizations. And so when there are those organizations and other areas, we want to try to get as many of them participating as possible.

Kris Pierce: So can you share some of the success stories with Simons have shared data?

Jennifer Tjernagel: SCN2A specifically, we’ve had many researchers request the data. Some have looked more in very detailed, in a very detailed way. All of the different information, for example, about the medical comorbidities, and how that might compare to data that they’ve already collected within their own lab.

I think that one of the things that’s really important is the network of families across the world, but also to really be encouraging networks of researchers to work together. Because it doesn’t always follow naturally that research labs are reaching out to other research labs looking at the same condition, unless there’s some opportunity to do so.

And I think maybe using a common source through the dataset or the samples, and then having conversations about it, whether those start at actual in-person meetings with the patient advocacy groups that are very powerful in bringing researchers together for a common cause. So I think that the collaboration both from patient advocacy groups in different countries, as well as research lab groups in various locations is extremely powerful.

Another success story that we’re just starting down the road on, but that was recognized within the past year or two is seeing what other resources the research community would need, and how we might be able to play a part in that. And one thing was many of the researchers were interested in looking at Induced Pluripotent Stem Cells, or IPSCs.

And one of the challenges is number one, it’s extremely labor-intensive and expensive to generate even a single cell line from a single patient in this type of cell line. But also, if they’re done in different labs with different protocols in how they actually create the cells, it can be difficult to compare those across different labs if they’re, if different, if they’re being created under different conditions.

So one way that we’re trying to collaborate and provide resources for these researchers is to create a central repository of these cell lines that are done in a consistent way. And that can be shared not only within a genetic group, or disorder group but also across different related disorder groups. And I think not only, we’ve not only been able to talk to researchers about trying to get priorities, but then also getting down to the level of which variants within a genetic change that they would be interested in studying.

And we’ve even started getting questions from researchers that are looking for specific genetic variants that we don’t yet have a sample for, but we have the ability to go out, do outreach to families who have already joined Simons, whoever joined Simons Searchlight to get those samples collected for researchers.

Dr. David Cunnington: So that’s a really interesting work. Another important player in this space is the pharmaceutical industry, and you know, they’re important in terms of getting treatments to market. Sometimes that can be hard for patient organisations to deal with. You know, they’ve been behemoths. Can Simons Searchlight play a role, or is there an ability to do that collaborative research and link those groups together?

Jennifer Tjernagel: We actually have started in the space with SCN2A fairly early on actually. I think one of the benefits of having the Simons Foundation involved is that we really are a neutral player, just wanting to see overall progress into the genetics into these conditions.

So one, we were approached by Roche Pharmaceutical, who was very interested in looking at the loss of function and gain of function, different variants within SCN2A. And they had proposed a project that was going to be an in-person clinic visit. I think it was a multi-day type, so very deep phenotyping, including EEG. And one of the things that was very important and that Roche definitely agreed to is the importance of sharing that information back and making that part of the pre-competitive space where we’re all trying to learn from that.

And I think that was a really good powerful message to be able to send is that even for pharmaceutical or biotech who ultimately, might, you know, are in the for-profit world, there definitely is a collaborative space where we can work together and help so that that data was shared back to Simons Searchlight. It’s available for any researcher who’s interested to download and look at in more detail. And we really hope that there are going to be many more opportunities to do that in the future.

Dr. David Cunnington: Yeah, that’s really great collaborative work and a nice example of how you can bring those different worlds together for everybody’s benefit.

Jennifer Tjernagel: Absolutely.

Dr. David Cunnington: So congratulations on the work that you’re doing and what you’ve been able to guard Simons Searchlight to be able to do over the last 10 years with your work there.

Jennifer Tjernagel: Yes, it’s been a -wonderful experience. I’m really looking forward to what the next 10 is going to look like.

Dr. David Cunnington: So, that was a really interesting interview, Kris, and really brought out a lot of the work that’s being done by Simons Foundation and Simon Searchlight. And also interesting to again hear the difference between the registry and the natural history study, and how they’re a bit of a continuum. And by expanding the database of what Simons Searchlight’s doing, it really is providing a very rich resource for researchers.

Kris Pierce: Yeah, that’s important. There’s that bilateral sharing of data. It’s very important to the patient community that information is being shared, and that we don’t have to overlap, in providing that information.

Dr. David Cunnington: Yeah, and it absolutely saves a lot of time. And what we all want is his development of treatments, the development of a cure for these rare and devastating disorders. And providing these platform types of technologies like Simons Searchlight and the Simons Foundation are doing is a really important part of that.

If you want to hear more episodes of the podcast, subscribe via any podcast app, and follow us on social media, Facebook or Twitter, or SCN2A Australia. Thanks a lot, Kris.

Kris Pierce: You’re welcome.

This podcast is not intended as a substitute for your own independent health professional’s advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider within your country or place of residency with any questions you may have regarding a medical condition.