Translational Science with Dr. Joni Rutter

What is translational science and how does it impact our CARRA community? To answer these questions, we turn to Dr. Joni L. Rutter, the Director of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). Tune in to hear about how she’s focused on breaking down barriers and speeding up the time it takes to get treatments from the lab to patients. Join us to learn about what translational science means for pediatric rheumatology, why it’s so important for rare diseases, and how data science could be used to help find treatments for rare diseases.

Transcript

Episode 9 of The CARRA Podcast: Translational Medicine with Dr. Joni L. Rutter 

Claudette Johnson: What is translational science and how does it impact a patient like me?

Dr. Joni L. Rutter: It's great to start off right there at the top. Translational science is really about turning research discoveries - basic science discoveries in the lab that a lot of the researchers do across the country - into real world health solutions.

Translational science does it in a way that really makes that faster and more efficient. How we do those translations from basic science applied to patients in the clinic? You can think about it as sort of like building a bridge between research and patient care. Scientists often call this the “journey from bench to bedside,” meaning that we start with basic discoveries, like identifying a gene that's linked to a disease. And, then we move toward treatments like a new drug or a new therapy. 

The thing about translational science is that it sounds kind of straightforward, but it's really not; it's not simple at all. It's full of roadblocks, delays, inefficiencies. Science is really hard and not only is science hard, but the way that we do science sometimes requires working with different groups or different companies or different organizations. And sometimes even just figuring out how to build agreements to work together can be long and complicated. So, translational science really works to clear those, all of those roadblocks, whether they be scientific or operational or administrative. And we want to make the process as smooth and fast as possible.

Dr. Joni L. Rutter: I think a key feature of translational science, too, is that it is disease agnostic. So, when we're talking about rare diseases, for example, there are over 10, 000 rare diseases. If we focus on any one particular disease at a time, it'll take us thousands of years to really be able to find treatments for all of those different rare diseases. So, we don't focus on just one disease. Translational science is about focusing on all of them. And we do that by tackling common challenges in research and in health care that could affect many different conditions. For example, we develop platform-based technologies, which are tools or methods that can be used across different diseases. Those platform technologies are called platforms because we might build them using one particular disease. When we're done building those tools. (those platform technologies), they can be a applied across many different diseases.

Dr. Joni L. Rutter: So things like gene therapy platforms or drug screening tools that can help accelerate progress for a wide range of health issues from rare diseases to common conditions to cancer or heart [00:05:00] disease, for example. That's why those tools are so important. And you know, your last part of your question – “Why does this matter?” - is really the crux of the matter.

Dr. Joni L. Rutter: Why? And that's because time is critical. Patients are waiting for better treatments, and translational science can help deliver solutions more quickly and broadly making an impact across many different rare diseases and, and hopefully improve our health. 

Claudette Johnson: I hear you talk about so much about speed from patient feedback and just getting the research there to where it needs to be to make impacts on the patient. How are some ways that you have found really help people cooperate and work together to get these outcomes in a quicker manner?

Dr. Joni L. Rutter: Getting people to work together — I think it's kind of a sweet spot for translational science. We equate the term translational science a lot with team [00:06:00] science. A lot of the ways that we try to bring people together to work on problems around, like for example, rare diseases, is that we bring we bring basic scientists, we bring clinicians together, we bring researchers together. And importantly, we also bring the patient and patient advocacy groups together as well.

Dr. Joni L. Rutter: And we get together and we talk about, you know, what are the key things that we really need to solve together? And by connecting the right people, I think that's where the innovation of what we can do for rare diseases is so impactful. With translational science, bringing together those, those different groups and sharing those ideas, we can make breakthroughs that, that wouldn't happen or wouldn't have even worked otherwise, because we have so many different facets of the research questions being covered people with different expertise and different backgrounds.

Dr. Joni L. Rutter: So it's about focusing on what on what works [00:07:00] and then learning from different groups of people, especially the patients; the patients know a lot more about the disease than anybody else does. So listening to the patient is probably the most critical thing that we can do. And they can let us know whether or not we're on the right track or if that's the right outcome we should really be thinking about. And that helps us then really guide the research into directions that will really help improve the clinical outcomes that we're looking for those patients. 

Claudette Johnson: So, you mentioned gene therapy. I was wondering if you could talk a bit more about how translational science fosters innovation into rare diseases specifically. Is this about learning from one rare disease and applying it to another disease? 

Dr. Joni L. Rutter: Yeah, exactly. So, for gene therapy, for example what we do is we, we take a page from viruses. So, there's a virus called adeno-associated virus, and it is a virus that has DNA in it. And, and what we do is we take its own [00:08:00] DNA out of the virus itself. So, it's kind of left with a shell and it has sort of a capsid that is what we use for gene therapy. There are a couple of viruses out there that are used, but I'm going to, I'm going to talk specifically about this adeno-associated virus and what we do with it in the sort of translational science arena is that for particular rare diseases where a gene therapy might be very effective. We use this virus and we say, okay, this virus, there are a couple of different flavors of the virus and, and one flavor might go to muscle. Another flavor of the virus might go specifically more to, to nerve cells. Another flavor of the virus might go to the liver. So we, we make sure we have the right virus that's going to go to the right cell type of the particular disease that's, that's, that's affecting the rare disease. And we put the functional copy of the [00:09:00] gene that has a mutation in it from, from the patient. And that, so, so with the adeno associated virus, we take its own viral DNA out and we put a functional copy of the gene that needs to re, be replaced in the virus.

Dr. Joni L. Rutter: Then we inject that virus into the patient and the virus then goes to the right cell types and it delivers a functional copy of that gene that is, has a mutation in it otherwise. And that functional copy then is able to be infected into the cells because the virus does what a virus does. It goes to the cells, and it starts replicating itself and creating functional copies of that gene or the protein product of that gene so that the cells start to function normally. And so in a sense the way that we create a platform tool out of this is essentially by using the adeno-associated virus vector or shell of that virus as the platform tool [00:10:00] where we can put different kinds of genes that are causing different types of diseases.

Dr. Joni L. Rutter: Because there are different flavors, we can go to the right cell types and we can deliver the functional copies of those genes and then the virus will then replicate itself and so there, it's theoretically sort of a one shot and completed in terms of treating that that specific disease. And so you can imagine that if we can develop those adeno-associated viral vectors that we can develop different flavors of those in different sizes.

Dr. Joni L. Rutter: That then becomes a platform for us to insert many different kinds of genes that would be useful for gene therapy for a variety of different rare diseases out there. And that's why we think that it's a really strong opportunity for the scientific community to really push on that idea to get more of those gene therapies out there to many more different rare diseases.

Claudette Johnson: How important have you seen communication be in your work? 

Dr. Joni L. Rutter: Communication is critical, you know, a lot of times that that's where a lot of the points of breakdown happen is if we're not communicating well together. So, one of the key activities of what we do as well, as I mentioned that it's not just the scientific questions that can be kind of pesky. It's also those operational things that can be kind of pesky. And communication is one of those areas. So, what we try to do is we develop partnerships. When we have partnerships with companies or with patient groups, for example, we develop agreements if you will. And those agreements are really important because they outline, for example, what role or responsibility one group has and what role and responsibility another group has in the way of working together to meet a common problem that we're working on.

Dr. Joni L. Rutter: One way to develop those communications is [00:12:00] to make sure that we have those agreements, you know, really done up front so that everybody is on the same page about what to do now. That's good, but it's not always the only thing that we need. You know going to meetings where we see patient advocacy groups and patient groups and intersections with the scientific and research community and enable those kinds of discussions to happen. These meetings are very important. Workshops are very important. Also just kind of updating the community through town halls or newsletters and things of that nature.

Dr. Joni L. Rutter: Those are some of the things that we try to do to help with communication. I think that's, you know, it's always around communication that I never feel fully satisfied that we've communicated, you know, everything that we possibly could to everybody who needs to hear it. But, but the venues for that communication are not always straightforward and people get information from [00:13:00] very different places. So, we try to do our best in using social media, using, using working groups and scientific meetings, and then also just the development of programs and making sure we bring the right people to the table. We try to capture it in many different ways. 

Claudette Johnson: Listening to you speak, I kind of feel like this podcast is a sort of translational version of how to bring the Patients to understand more about the scientific community. Knowing my audience, how would you say translational science has impacted the CARRA community specifically? 

Dr. Joni L. Rutter: Oh, yeah, that's a great question. CARRA is already doing incredible work, bringing together researchers, doctors and families to tackle pediatric rheumatological diseases. I think translational science can help [00:14:00] supercharge those efforts by taking what CARRA learns and what it's been doing and helping to transition that into action. So, for example, when CARRA collects data from patients. As you know, CARRA has a registry, and translational science can help turn that data into possibly new clinical trials. For example, identifying patterns in the data and understanding how certain treatments might be able to work and figuring out how to apply those insights into developing better therapies for all kids, not just the ones in a particular study. So, I think those are ways in which I think translational science could really advantageous for not just the CARRA community, but all communities. 

Claudette Johnson: Now, to the rare disease [00:15:00] families listening to this, what is your call to action? 

Dr. Joni L. Rutter: My call to action is you know, really here's where the CARRA community comes in is supporting translational science. It isn't just something that scientists or policymakers do. It's something that we all need to do together. We all need to be part of the translational science and that, you know, moving the research insights that we find into that clinical practice. So, the call to action I would say is, you know, really advocate when you talk to your community. Encourage your community to talk to your policymakers, your Congress representatives, and share your story. Remind them that funding translational science directly impacts your family's future. And it's important for us to make sure that we critically move the scientific findings that are generated into that clinical practice. And that's one thing that you can do. I'd say the other thing is that you can participate and join studies or [00:16:00] registries like the ones that CARRA leads, as you mentioned. Your contributions and your family's contributions are just invaluable to that. And I guess, the last call to action I would say is, is really stay engaged, you know, learn more about how science happens, why science matters, why translational science matters to bring the basic science findings into the clinical setting.

Dr. Joni L. Rutter: Because knowledge is power and when you're advocating for, you know, your specific disease or your specific family member there's nothing more important than ensuring that what you're doing is going to help contribute to ultimately getting those treatments to the people who need them. So, at the end of the day, I'd say it's, you know, translational science isn't just about the research.

Dr. Joni L. Rutter: It's really about the hope. So when you advocate, when you participate, when you're engaged, that's what brings that hope alive. And it's about turning the challenges that you're facing today into the solutions that will make tomorrow better, not just for your family, but for all families who are dealing with [00:17:00] pediatric arthritis and rheumatological diseases.

Dr. Joni L. Rutter: And who knows those insights may help find a variety of other or help a variety of other diseases, as well. 

Claudette Johnson: Also, another topic that I wanted to touch on is, I know this is something that you've been working on for years, but how important is diversity and diverse patient groups when it comes to scientific research?

Dr. Joni L. Rutter: Yeah, it's such an important question. You know, when we think about diversity, there are so many different ways that we need to think about it. A lot of times, the clinical trials, for example, are done in non-pediatric patients. We do initial clinical trials in adult populations to understand safety of particular medications that are, that are being used in clinical trials.

Dr. Joni L. Rutter: I understand that and it's not a bad approach, but we want to make sure that we're inclusive of the pediatric population, too. And we want to ensure that we understand from the pediatric patient population, the importance of [00:18:00] studying those medications in them as well. So, it's important to make sure that we have the diversity of the ages that are going to be representative of the diseases that we are studying.

Dr. Joni L. Rutter: The ages, the demographics of the population are critical as well. We want to make sure that the results that we get from any research that we do can be generalizable to as many populations as possible. And doing that means that we have to include as many populations as possible. And so that diversity is critically important to the research that we do at in what we're doing at NCATS is thinking about that, not just on the clinical side, but also on the pre-clinical side.

Dr. Joni L. Rutter: In the preclinical side, we, we focus mainly on cells. We study in vitro cells and we look at how. Potential therapeutics that we think might be helpful for a specific disease. We understand how they work in cells first. [00:19:00] And so they're not in any patients just yet, but we test them in cells.

Dr. Joni L. Rutter: That's usually our first clue as to whether or not a particular therapeutic might be or a potential therapeutic might be toxic to cells, and that's where we might learn about safety or whether or not they actually see the result that we expect. Do they actually help the cell get better? If it's something from a patient population where it might be missing some critical aspect of the cellular function, and if it gets better, then we think, well, that might be a clue that this particular therapeutic might be something that is efficacious in clinical trials.

Dr. Joni L. Rutter: So, we study them in cells first, and it's important at that stage too, to make sure that we're using cells from a variety of different populations as well, ensuring that we're pulling from pediatric populations, adult populations, elderly populations, and then populations of diverse [00:20:00] backgrounds.

Dr. Joni L. Rutter: So, those are some of the other ways in which we're trying to address even more of that up front in the preclinical work that we're doing so that we can be more predictive about how those potential therapeutics might work in the clinic if they make it past our sort of initial experimentations, then that tells us that they might work in the clinical populations.

Dr. Joni L. Rutter: That's not always a given though. In fact, nine times out of 10, they fail in the clinical side. So, we're trying to actually build a more robust, predictive preclinical pipeline so that it can better inform what happens in the clinic. 

Claudette Johnson: As you said earlier, you're helping to direct research in more than 10,000 rare diseases. What are you most excited about? 

Dr. Joni L. Rutter: Oh, that's a good question. There's so many things I'm excited about, Claudette. So, you know, I think one of the big picture things though is, you know, with 10,000 rare diseases, I think one of the biggest areas is data science and artificial intelligence and being able to use data in ways that we've never been able to use before. One of the things that I think highlights the power of data science is that we're able to look at data from a variety of different rare diseases, for example, through looking at data from very different databases. And we're able to use artificial intelligence and machine learning with humans in the loop, of course, doing that, to look at patterns within the data to see if there might be potential therapeutics that are already known, already being used. Maybe they weren't used for the particular rare disease that we're looking at. But for some reason we think they might because we found a new pattern in the data using artificial intelligence and AI and machine learning to identify it. So, for me, I think one of the most exciting areas is how [00:22:00] we can leverage the deep knowledge that we can see through pattern recognition in the large data cohorts that we have or large data sets that we have to help us identify insights that we never would have known before or been able to really detect before without sort of that really deep pattern recognition through AI and machine learning. So that's one area that I'm pretty excited about.

Claudette Johnson: But all the data and AI only works if patients take part in the research, right? 

Dr. Joni L. Rutter: Exactly. And it's taking part in the research and making sure that we can get as much as we possibly can. So, you know, it's important for us to make sure that we reach out to the patient communities to let them know to take part in registries, to participate in studies. We're also hoping to engage the international community. Rare diseases, you know, they know no boundaries and perhaps we can get more data by also encouraging the international community to take part as well. 

Claudette Johnson: Dr. Rutter, thank you so much for such a fascinating conversation. [00:23:00] We really appreciate all the work you're doing.

Dr. Joni L. Rutter: Claudette, thank you. Thank you so much for your interest and a big shout out to the CARRA community. Thank you so much for having me on your podcast.

Claudette Johnson: Is there anything that we left out that you'd like to cover, us to cover anything? 

Dr. Joni L. Rutter: You know, I guess the only thing I would say is, you know, we talked a little bit about the whole 10,000 rare diseases and our mission, our goals over the next decade are to, you know, really use that 10,000 rare diseases as, as the big mantra of how we can bring more treatments for all diseases more quickly. And that's important because right now with 10,000 rare diseases, we only have 5 percent of those diseases that have treatments or cures. So, 95 percent need our help. And one of the things that we really want to do is see a five-fold [00:24:00] increase in the number of diseases with treatment. So, that's 5 percent that I mentioned before now moving to 25%.

Dr. Joni L. Rutter: And, I think with kind of some of the things that we talked about today, like gene therapy and data science and et cetera, I think that these sorts of tools can really help us move the needle on rare diseases to get that number up. We may fail at the 25 percent number in 10 years, because it's a really hard, hard area, but I would rather fail at 25 percent than succeed at 6.

Claudette Johnson: In many ways, this podcast is an example of translational science. Connecting doctors, researchers, with you, the patient. And that is why we want to hear from you. Head to the CARRA podcast page and leave us a Speak Pipe message.

Claudette Johnson: CARRA is the Childhood Arthritis and Rheumatology Research Alliance. We are doctors, researchers, and [00:25:00] patients all working together to prevent, treat, and cure pediatric rheumatic disease. We encourage you to share the CARRA Podcast with friends, patients, and anyone else interested in learning more about the incredible work of the CARRA community, dedicated to creating a world free of limitations for children with rheumatic disease.

Claudette Johnson: This episode was produced and edited by Mason Lippman. Our music is by Jonathan M. Horner. Thank you for listening.