A Deeper Look at Immunotherapy Research with Jessica Dunne
Jessica Dunne is a Senior Director of Research at JDRF, focusing on prevention of Type 1 diabetes. Recently she spoke with Beyond Type 1 about what it means to prevent T1D, the importance of population screening, exciting trials currently underway and more. This interview on Type 1 Diabetes Research was created in partnership with JDRF through the JDRF – Beyond Type 1 Alliance.
Can you start by telling us a little bit about your background and how you got involved with JDRF?
My undergrad and graduate degrees are both in the field of biomedical engineering. I spent some time working in industry and I sort of wound up here at JDRF a little serendipitously. It was 2008 at the beginning of the stock market crash and I was working at a small biotech firm and long story short — it didn’t last. I wound up having an opportunity at JDRF and at another pharmaceutical company. And I chose JDRF because I wanted to do something that was more mission-driven.
When we talk about prevention of Type 1 diabetes, what exactly are we talking about?
I think the vast majority of previous efforts at preventing Type 1 have been immune-focused, but we’re also taking a little bit broader view. So things like beta cell survival agents are probably also relevant here. We’re also looking at agents that are being used in metabolic control. If you alleviated some metabolic stress, could that help delay diagnosis too? So we’re a little agnostic in terms of the way we approach it.
We are also considering preventative agents that target environmental triggers, such as a virus or agents that promote microbiome-based immunoregulation and permutations of those. If we’re thinking about a real curative therapy, it will likely be a combination therapy, perhaps an immune plus beta cell therapy. And then if we’re thinking about delaying progression to Stage 3 disease, then perhaps one or the other is sufficient.
How important is population-screening for T1D?
This is one of the things I’m probably most passionate about. Our focus here at JDRF is on universal screening, for a number of reasons. I think it really has the ability and the possibility to change public health. We know that a large percentage of kids, especially in the U.S., get diagnosed in DKA and that screening and monitoring programs have the ability to curtail those numbers.
In the absence of an approved therapy for Type 1 prevention, we strongly believe that reduction of DKA at diagnosis has benefits both in the short term and in the long term. In the short-term, benefits are really centered around avoidance of DKA itself. Further, we know that DKA avoidance also has cognitive benefits, both in long term and then short term. It has also been shown that avoidance of DKA at diagnosis has a long term impact on A1C numbers.
While we all agree that A1C numbers aren’t the end all and be all, but they are an important part of glucose control. And we know that better glucose control leads to better outcomes in terms of complications. It’s our belief that if we could avoid DKA diagnosis, it may also have real impact on long term complications as well. So again, in the absence of an approved therapy, we’re strongly pushing that.
Who would you advocate screening? Family members? Children? Everyone?
Only about 10% of people newly diagnosed have a family member with Type 1. And so, in order to capture the vast majority of kids who will go on to develop T1D, universal screening in childhood must be implemented. I think the other reason I say in childhood is because one of the things that we are keenly aware of is that we don’t have a good handle on adults who develop Type 1 and when they develop antibodies, whether it’s at younger ages or whether it’s older in life. Probably based on the data that we have at hand, both of those things are true.
What this means is that some adults develop autoantibodies earlier in life when they’re in childhood and just progress more slowly to Type 1 and some of them develop autoantibodies and start progression later in life. But we don’t have a good handle on that. So, I just want to make that distinction that we’re probably still going to miss some people who develop Type 1 even if we do universal screening in childhood. It’s an important question that we often ask ourselves about adult-onset population. I think that’s probably a whole separate conversation.
For the near future, we need to understand how to transition studies like Fr1da and ASK into the public health and out of clinical research.
Are there different types of T1D?
That’s an excellent, excellent question. I think for sure there’s heterogeneity in disease much like there is in every other disease. We know that in other diseases, not everyone will
There was a publication early in January in Diabetes Care talking about endotypes. I fundamentally don’t like the term endotype and bucketing people into specific endotypes, partly because I think it’s going to slow down drug development, and partly because I believe in a more continuum-based approach. But the other reason is that the best success we’ve had so far is Teplizumab and it’s a bit of a hammer on the immune system. So, let’s start there.
Okay, now we’ve got an immune therapy that works. It doesn’t work in everybody. It works on a lot of people. Let’s figure out why it works in certain people and build on that success. This is a fundamentally different approach than starting at slicing and dicing.
Any specific trials you’re excited about getting the results to?
The results from ATG-GCSF trial, again a little bit of a hammer approach, in the newly onset T1D were pretty exciting. And I think now that the idea is to step back and look at prevention trials as well.
One of the other trials that’s ongoing and interesting is the anti-TNF trial with Jansen called T1GER to try and preserve beta-cell function in children and young adults with newly-diagnosed T1D. Like Teplizumab, this is exciting because you have an industry partner behind it. If there are positive results, then there’s also maybe more of an incentive to further develop it.
And so I think there’s a lot of excitement. I think there are a lot of different types of approaches that people are taking, which is really exciting because it’s spurring development in this area, fueled by some recent successes. We are taking a multi-faceted approaching to curing and preventing T1D, which hopefully means we’ll get there sooner!
To learn more about all the great T1D research being funded by JDRF, visit their research and impact page here.