In this interview, Steven Gray (University of Texas Southwestern Medical Center), recipient of an ASGCT 2019 Outstanding New Investigator Award, discusses his research and what the future holds for gene therapy.
Please introduce yourself and your institution?
I did my PhD at Vanderbilt University (TN, USA), in Basic Cell and Molecular Biology, and then went to University of North Carolina at Chapel Hill (NC, USA) to train with Jude Samulski, specifically in AAV vectors and gene therapy. In December 2017, I came to the University of Texas Southwestern Medical Center (TX, USA) to try to build a large gene therapy program. We’re aiming to move things to the bedside and facilitate close collaborations between preclinical researchers and physicians, especially in the area of pediatric neurology. Our goal is to work with patient groups, trying to apply gene therapy to any disease where it makes sense and move therapies rapidly into clinical trials.
“…[advocating for patients]should be the center of everything that we are doing in the field of gene therapy…”
What is it that most interests you about gene therapy?
I was interested in gene therapy when I first heard about it in the late ’90s, as an undergraduate at Auburn University. I was interested in studying it at grad school but decided to approach it from a different direction of just learning to be a good scientist before applying that knowledge. After graduate school, I still thought about gene therapy so once I got my PHD I wanted to move into the field.
You were awarded the “Outstanding New Investigator” award by the ASGCT at ASGCT 2019. What does this award mean to you?
I am really humbled by the award; it’s a fantastic recognition by the society. I see so many other people in the society and the gene therapy field who are doing absolutely fantastic work, and I think it was fantastic that they chose me but there are lots of other people that they could have chosen who would be very deserving of the award.
“this is the beginning of what we could call a “treatment evolution””
I really appreciate the recognition of my role, which is not just doing good science but being very passionate about trying to bring these treatments to patients and trying to really advocate for the them. I think that should be the center of everything that we are doing in the field of gene therapy where most of us are working with rare diseases. I think the award recognizes the roots of gene therapy, which is trying to serve these patients that are often in very desperate situations.
Your award presentation was on the brink of a treatment revolution for inherited pediatric neurological diseases. What’s the current state of the art for treatments for diseases like this?
There are certain pediatric neurological diseases, such as some of the lysosomal storage diseases, that are particularly amenable to gene therapy and I think if we can treat patients very early this could be a very comprehensive treatment. I am always very hesitant to use the word “cure” but I think that the existing technology right now has the ability to very transformative.
Beyond that are diseases where I think that the technology right now can be a treatment and could help patients, but it’s definitely not going to be a cure.
There is a lot of excitement around gene therapy and I think it’s very deserved, particularly for pediatric diseases where we really haven’t been able to do a lot for these patients. I think it’s created a lot of hope and it’s opened up a lot of doors to being able to potentially treat hundreds of different diseases. However, I think that we all need to recognize that whilst you are going to see some things coming out in the next few years where the treatment results are absolutely amazing and truly transformative, for the majority of diseases, with the technology we currently have, the treatments will fall short of this bar that has been set. So for me, this is the beginning of what we could call a “treatment evolution”: the truly transformative results we are seeing are just the beginning. Technology will continue to improve, and I think that those successes are spurring people to improve the technology and it’s going to be an exciting time in the years to come.
“I think we will look back at things like AAV9 and it will seem crude.”
When you refer to technology, what does this cover? Hardware, techniques or knowledge?
I think all of the above. When I talk about technology I am mostly talking about some of the viral vector technology. The gold standard right now is a vector like AAV9, and in the field of pediatric neurology and gene therapy I think you can divide it into the pre-AAV9 era and post-AAV9 era. However, I think that you are going to have new technologies which come along, probably very soon, that will help us make another similar leap. There are other things that are coming into play, such as better manufacturing technology, better management of immune responses and better delivery of the virus – all of these things can contribute to making things better and they all work synergistically.
Let’s look ahead into the future – where would you like to be in 4 or 5 years’ time?
I think we will be in a similar place where we are now; we will still be struggling to do more and do everything on a larger scale.
What we are trying to do now in some ways is develop an efficient pipeline to go from the disease, conduct the trials and commercializing the therapy to treating every patient in the world, all within an academic setting. That’s everything, so in 5 years I would hope that we have better infrastructure and better technology in place to be doing that in a more efficient way. I think that the regulatory agencies are also trying to figure out how to allow people to do this faster and easier but still in a responsible way.
That’s a lot to happen in 5 years, but everybody is working pretty hard on it. 5 years ago, we had the first gene therapy trial started with AAV9 for SMA and just look at where we are right now. It’s pretty amazing where we have come in 5 years.
What do you think is the future of advanced therapies?
Right now, the treatments that we are doing are not truly regenerative medicine; with gene therapy, we are doing things to slow or halt disease for the most part. Where I think we will probably start moving is answering questions like what are ways that we can truly do regenerative medicine, how can we offer hope to patients that have symptoms or that are further in their disease rather than just trying to intervene very early?
“I am always very hesitant to use the word “cure” but I think that the existing technology right now has the ability to very transformative.”
I think we still start to see merging of technologies include stem cells and gene editing, as well as a lot of things that we haven’t even dreamed about right now. Along the way, a lot of things we currently struggle with and which are bottlenecks, such as viral vector manufacturing will get better. I think we will look back at things like AAV9 and it will seem crude. It’s exciting that we are getting so much industry involvement, which will help with industrialization of processes, even if it can lead to more secrecy. The more common gene therapy becomes, the more trials start happening, the faster that things move.
However, something that I try to impress on any parent or patients that I talk to is that these are still experiments. There is all this pressure to move very quickly and there is this optimism that it’s going to work and be transformative, but once you start doing this on a large scale there will be things that happen that aren’t anticipated.