Research points to more convenient drug

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient," with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Researchers from Upstate took the top prize in a State University of New York competition for startup business pitches. They want to change how corneal injuries and the scarring that can lead to vision loss are treated. Here to talk about the team's work is Dr. Audrey Bernstein. She's a professor of ophthalmology and visual sciences, biochemistry and molecular biology and cell and developmental biology at Upstate, and she's co-founder of the DUB Biologics startup. Welcome to "The Informed Patient," Dr. Bernstein.

[00:00:46] Audrey Bernstein, PhD: Thank you.

Thank you so much for having me.

[00:00:49] Host Amber Smith: We want to understand your project, but first can you explain a little about corneal injuries and how they're treated now? How common are corneal injuries?

[00:00:58] Audrey Bernstein, PhD: Sure. Corneal injuries are actually very common both in the United States and certainly throughout the world. You can have an injury that is a mechanical injury, just as you would imagine -- something hits your eye. But there's a lot of underlying diseases that can cause problems with your cornea. So this can be what we would call a corneal ulcer, if you have an infection and it doesn't heal properly. Also, there's conditions that a lot of people have heard of called dry eye, and sometimes dry eye is just dry eye, and sometimes it progresses to where it really affects the top layer of your cornea called the corneal epithelium. And that causes problems with wound healing in the cornea if it advances to that stage.

So there's a lot of, actually, what are called indications of problems with the cornea. And, your cornea is the most highly innervated tissue in your body, and so, as everyone knows, when you get something in your eye or you have something wrong with your eye, it really, really hurts. So the cornea is a very specialized tissue, and we want it to work perfectly.

[00:02:14] Host Amber Smith: Do corneal injuries always cause scarring?

[00:02:17] Audrey Bernstein, PhD: No, they certainly don't. The cornea is made up of a few layers, and so the top layer is the epithelium, and we call the middle layer the stroma. And between those two layers, it's what's called the basement membrane.

So if you have just an epithelial, small scrape, it still really hurts, but it usually heals just fine. If you have a chronic condition where you're then upsetting the basement membrane and getting further into the cornea, that's where it really can start to have a scarring outcome.

[00:02:55] Host Amber Smith: So what happens currently for someone who has a corneal injury? How are they typically treated?

[00:03:02] Audrey Bernstein, PhD: So typically people are treated with the mainstay of steroids and antibiotics. The antibiotics are fine. The steroids have variable outcomes. Sometimes it works just fine, and other times it doesn't work, and it's very hard to predict which person, under which condition, will have which outcome.

In addition, steroids have the unfortunate side effect of producing higher over time -- not immediately, but over time -- higher interocular pressure. And that pressure in your eye is linked to the development of glaucoma, which is another eye disease. In general we would love it if we had a new therapy that closed the corneal wounds, prevented scarring and was not a steroid.

[00:03:58] Host Amber Smith: Yeah, that sounds great. Now, corneal injuries, how often do they lead to blindness?

[00:04:04] Audrey Bernstein, PhD: So that is a hard question to answer because it, to some degree, depends on where you live. If you're in a first wheel world country, there's still, unfortunately, a lot of people -- and I can get into what people do in that case -- but in third world countries, it's the leading cause of blindness because you don't have the interventions that you have here.

So what is the intervention? You can get a corneal transplant, and that's obviously not something that doctors do quickly. And it's not taken lightly. It's a tissue transplant, and although it has a reasonably good success rate, it's very tricky in terms of the outcomes and taking the medications that you're required to stay on over time and the potential of rejection later. So obviously, like any tissue transplant, if you can save your own tissue, that's preferable to having to go through a transplant procedure.

[00:05:12] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith, talking with professor Audrey Bernstein about corneal injuries.

Now, what can you tell us about the DUB Biologics project you're involved in?

[00:05:26] Audrey Bernstein, PhD: Sure. So we go by "DUB" Biologics. And this is an academic spin out or startup from my work. I'd say it's sort of at the end of 10 or 15 years of academic work and getting to a point in saying, "well, we think we have something that we can help people with."

So as of 2022, we started. I'm a co-founder in DUB Biologics. And we have a therapeutic, as we've been talking about, for the cornea, and we're now expanding into skin. So we think the things that happen in the cornea, very similar outcomes happen in the skin. And skin, we can also talk about diabetic wound healing, bedsores, et cetera. There's a lot of indications that have the same biological or similar biological underpinnings that our drug could address.

[00:06:21] Host Amber Smith: So do you work on the skin first before you try this in the eye, or have you already tried this in the eye?

[00:06:27] Audrey Bernstein, PhD: OK, so just to take this back a second. We do not have an FDA, we do not have an approved therapeutic. So that is a long road to getting approval to being able to go into patients.

So right now it's still in the world of academic research. I think within two years we will try to get FDA approval for patients. And from there, again, you have a long road through the trials for safety first, of course, safety, and then efficacy. So it's really a long process that's highly, highly regulated.

We are not there yet, but I agree that we might try in skin first for safety and go from there. So it's probably another 10 year road before you have a fully approved drug that's on the market.

[00:07:26] Host Amber Smith: So when you say a therapeutic, are you talking about a brand new medication, or is it a existing medication that you're using in a new way?

[00:07:36] Audrey Bernstein, PhD: This is a new medication. It is a topical liquid. When dropped on the surface of either the cornea or the skin, it will get into the cells. And it stops production of a certain protein that causes scarring and causes inflammation. So if we knock down that protein, we then can close the wound faster and avert scarring. And so the exciting part of this is most drugs, especially for the eye, need to be dosed frequently. And anyone who has any kind of eye problem, whether it's cornea, whether it's glaucoma, et cetera, they will tell you that they do not like the eye drops, because it's four times a day, six times a day, for weeks and months, and people hate it.

So our drug, our class of drug, enables you to have one drop. And it has efficacy -- which means it works -- for three months. So that's a big change. So that's what we think is a very exciting, would be a very exciting advance, again, after safety is established.

[00:08:49] Host Amber Smith: So is it working to prevent scarring, or is it working to promote wound closure, or both?

[00:08:57] Audrey Bernstein, PhD: Great question. So, the first thing, the two things are intertwined, because if you promote correct wound closure, then you avert scarring. And so the two things are very, very closely linked. And the reason is that your immune cells are critically important to stop infection, but if the immune reaction stays, and it turns into a chronic situation, this often leads to scarring.

So if you can close the wound quickly, and this is just generally true in your body, then you're going to avoid the infection. You're gonna lower your immune response. And you're going to prevent scarring. So it's really all linked together.

[00:09:43] Host Amber Smith: So do you think there would be any potential for it to be able to reverse damage that's already been done? Say somebody who had an injury and some scarring from months ago or years ago...

...would this work on that?

[00:09:57] Audrey Bernstein, PhD: That's a great question.

We don't have a lot of data on reversing. That's kind of the holy grail of any kind of therapeutic like this. It's possible that it could, and with other drugs there is some data to show that it is possible to reverse scarring and fibrosis. So I haven't used the word fibrosis a lot, but just to introduce it here, scarring is very similar to what people have heard of as lung fibrosis and liver fibrosis.

So, so far we've talked about topical things, cornea, it's the front of your eye, and skin, but are further things that we're thinking of down the line are lung fibrosis, and so that would be, for instance, drug delivery with the nebulizer. So that's where we get into not only preventing but reversing disease. So I don't have enough data to promise you that we can do this, but we are hopeful that it's possible.

[00:10:58] Host Amber Smith: Well, that is exciting. Now, the competition that DUB Biologics won is called the SUNY Startup Summer School. It's something that's held every year. Can you talk a little bit about the goal behind the competition and why you were involved in it?

[00:11:13] Audrey Bernstein, PhD: Sure. So our team, and I should have introduced this before. I'm a co-founder of DUB Biologics, and I founded this company with Tere Williams. She is the CEO. And she participated in a S4 summer class given by the research foundation. And this is sort of training for startup companies to understand, really, how to run a business like this, because these businesses are often started from academics who are scientists that don't have a tremendous amount of business experience. So it's really a training class, and it leads up to what's called "demo day," which is a what's called a pitch competition. You have a certain amount of minutes, six minutes or eight minutes, or a certain amount of slides to tell your story. And this is your story of, it's not so much a science story but it leverages the science, and it tells the business story, the potential that the therapeutic has and the potential of the business. And we were fortunate to be able to pitch in that competition, and we were winners that day.

[00:12:25] Host Amber Smith: It sounds a little like (the television show) "Shark Tank."

[00:12:27] Audrey Bernstein, PhD: It's exactly like "Shark Tank."

[00:12:30] Host Amber Smith: What were some of your competitors? Do you remember any that piqued your interest, or did you even hear any of the others?

[00:12:36] Audrey Bernstein, PhD: We heard the others. You know, there's a wide, an incredibly interesting, wide variety of technologies having to do some therapeutics, some batteries -- there's a lot of interest in improving energy sources -- some had to do with online teaching platforms. So it's a very varied group. It's not just based on therapeutics.

[00:13:04] Host Amber Smith: Well, I know you talked about -- I mean, this is a long-term thing. It's not like there's going to be a product on the shelf tomorrow, and it's step by step through the FDA before you can even get approval -- but where are you scientifically? How far out are you from clinical trials, say?

[00:13:20] Audrey Bernstein, PhD: It is a very long road. And as I said, we've done a lot of years of research in the lab. In terms of the company, though, we're really at the beginning stages. Our hope, and I think it is realistic, that we could have approval for a pilot study in people in two or three years. And then from there, it all depends on, again, safety and efficacy. But you have to go through the clinical trials with large numbers of people and to figure out if it is safe and effective. And so that is a long, a long term project, as I said, about 10 years. But I do think in two or three years we will be into our first study in patients.

[00:14:04] Host Amber Smith: Well, very interesting. Well, congratulations, and thank you so much for making time to tell us about it.

[00:14:09] Audrey Bernstein, PhD: Thank you so much. I enjoyed talking to you.

[00:14:12] Host Amber Smith: My guest has been Dr. Audrey Bernstein. She's a professor at Upstate in ophthalmology and visual sciences, biochemistry and molecular biology and cell and developmental biology, and she's also co-founder of DUB Biologics. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. If you enjoyed this episode, please tell a friend to listen too, and you can rate and review "The Informed Patient" podcast on Spotify, Apple, YouTube, or wherever you tune in. This is your host, Amber Smith, thanking you for listening.