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Future Proof Extra with Jonathan McCrae, proudly
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supported by Research Ireland on News Talk. Welcome back to Future Proof. I'm Tara Schein standing in for Jonathan McCrae. This week, Dublin hosted a major international conference on cystinosis with experts from around the world speaking about the condition and how it can best be treated. So what exactly is cystinosis and how can we help patients with the condition? Anuj Chauhan is a professor of chemical and biological engineering at the Colorado School of Mines, and he's in Dublin to speak at the conference. Anuj, you are very welcome. Thank you for joining us.
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Oh, of course. Thank you for having me on the show.
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And listen, just to get started, I had never heard of cystinosis. What is it? And how many people are living with this condition?
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Yeah, great question. In fact, I hadn't heard of cystinosis either until I started working on this disease. There are only a few thousand patients worldwide, just about 500 in United States, which is where I'm from. So, yeah, it's a disease. That's why it's sometimes referred to as orphan disease, which means very few patients. This is a genetic disease. That means you're born with it. And the patients that are born with it, they lack a certain clearance mechanism in their cell and due to which crystals accumulate in their cells. So there is an amino acid called cysteine, and all of us have that cysteine. And normally that cysteine, it can clear out of lysosomes in the cells and come out. But because these patients lack that specific gene, they accumulate inside and form crystals.
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So how does that impact on patients having crystals forming inside you? Sounds painful, right?
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So these crystals can form in many different organs. It's called a systemic disease, which means it really happens in all organs. But certain organs are more susceptible to this and especially kidneys and eyes. So kidney is actually the biggest problem because typically these patients, they eventually need to have kidney transplants. The age at which they have kidney transplants depend upon how good the therapy was they were taking. There's a drug approved for this treatment called cysteamine. And if you take that well or with good compliance, you actually can live with your original kidneys for a long time. But eventually, most patients eventually end up with creatine transplants. Also, these crystals form in the eyes, which are. You can see actually very clearly those crystals, and they do form. And if you don't clear them up, eventually you could potentially lose eyesight. And therefore, this drug has to be taken by eye drops. Because what happens is when you take the drug orally. This drug can go to every other organ in the body, but not the eyes, because eyes, they don't have blood vessels because you need to see through the cornea. And so to treat the disease in the eyes, you have to separately take eye drops. So, yeah, so these patients have to take oral therapy as well as eye drops.
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As well as eye drops. And just to kind of think about how you got involved in this as well. So you're an engineer, I believe you're not a medical doctor. So how did you get involved in this work?
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Right, great question. So I'm a chemical engineer. Chemical and biological engineer, which means I really work on a lot of biological problems, including drug discovery. But the way I got involved in this is because of the organization Cystinosis Ireland, which is organizing this conference as well, or at least in collaboration, they're organizing this conference. They're this amazing organization that really take very good care of all the cystinosis patients in Ireland. And so the work I was doing was on delivering other drugs by contact lenses to eyes. And especially we're looking at glaucoma. We're looking at treating infections. And when Ann Marie Doubt, she was, I think, the president of the organization here, she reached out to me and asked me that what you're doing seems very relevant to our patients. We would love to see if we can work together. So I took that opportunity. And since then, I've been working with Cystinosis Ireland. So, yeah, that's how I got involved in this.
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So as I understand you were explaining earlier, one of the treatments, particularly for eyes, is eye drop. So is that effective? Is that working for patients at the moment, or what is it that you're trying to improve?
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Right. So the eye drops are actually working, and that's great. But the problem is you have to put them eight times a day.
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Oh, wow.
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For one of the formulations. And then there's another formulation recently approved, United States. It was already available in Europe for a long time, which has to be done four times a day. But there are some other problems with that because it's very viscous. So when you put it on kind of, you can't see very clearly for a long time. It's difficult to put in. So while the drug is effective, there are some deficiencies in the way we are delivering them by eye drop. So that's what we are trying to address. The way we are trying to address it is by loading the drug into contact lenses. Because what happens is if you put an eye drop in the eye, you might think you're putting the drug in the eye, but what happens is when you blink, a lot of that drug ends up in the nose. Because the tears, every time you're blinking, you're bringing in new tears to the eyes. And the tears that are in the eyes, they get pushed towards the nose. That's the clearance mechanism to keep the eye very clean. So the drug that you put in very quickly ends up in the nose. Also, when you're blinking, the back of your eyelid, there are blood vessels there, you can see that. If you flip the eyelid, you see it very red. So the drug also goes through those blood vessels into the body. So while you think you're delivering drug to the eyes, and yes, a small percentage, about 1% or less is going into the eye, remaining 99% is actually going into the blood. So in fact, an eye drop is a good way to deliver drug directly to the blood. Now the 1% that does go, it does have therapeutic effect, but, but nonetheless you can do better with a contact lens because as you can imagine, because the contact lens is just sitting on the eye, more amount, more percentage goes into the eye directly, but also you can do sustained release. So like as I said earlier, that eye drops you have to put eight times a day. If you keep the contact lens on for the eye for about two to four hours, because the drug is coming out slowly, you can essentially get the same efficacy at eight eye drops with no single contact lens. So it'll be much easier for the patients to use and hopefully even better in terms of therapy.
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And so the idea is this is a contact lens that people would wear just daytime in their normal day to day life, and it would be gradually releasing the drug into their eye.
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Exactly, exactly. That's what it is. Now we are right now thinking that maybe patients wouldn't want to wear it for the whole day. So we are designing in a way that only two to four hours wear, it will be sufficient. But yes, if you need vision correction, these contact lens could potentially also have vision correction, although we haven't completely decided if that would be the way to go. But nonetheless, you can wear it for a longer time, but two to four hour wear would be enough to get the therapy you need.
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And so how have you been developing and testing these contact lenses?
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So the way it starts is you first try to do bench scale testing to make sure that you can get the drug into the contact lens. You can get it out because you want sustained release. If the drug comes out within Five minutes, it's not useful. So you have to design the lens so the drug comes out at a controlled rate for whatever duration you want. You also want to make sure sufficient drug is going in after you think you have the design all worked out. You test the lenses in animals, and typically we use rabbits, although in some studies we also use dogs. And with animal studies, you prove safety, you also prove efficacy by showing that, yes, you're getting the right amount of drug into the ocular tissues. You're also able to dissolve the crystals in the eye. When all of that is validated, then you go to the regulatory agencies and you apply for what is called, at least in the United States, it's called Indigenous Investigation New Drug Application. And when that is approved, you do the studies. And, yeah, if those studies all work out in humans, eventually you get the NDA, which is the new Drug application, and then you're able to sell the product to the patients.
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I think I read in some of the notes as well that you were, you know, moving on from using live rabbits to using the eyes of, like, cadaver rabbits as well. Was that something you looked at?
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Right, yeah. So when you're testing for a disease, you need the animals to have the disease. And cystinosis is a disease that rabbits don't have, and that's a good thing for the rabbits. But it doesn't quite work out for us because then we cannot show that the drug is efficacious. So therefore, what we did was we created an animal model by depositing the crystals into the eye. And for that, instead of using live rabbits, we chose to use cadaver rabbits just because, you know, a live rabbit was necessary. So in that case, yeah, we took cadaver eyes and we loaded those with crystals by depositing the cysteine in there. And then, yeah, we showed that there are contact lenses. We can actually dissolve the crystals.
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One other thing I was wondering about is. So you've spoken in particular about how this disease affects eyes and the liver, kidneys. Kidneys. Thank you. What about, are there other organs where it has a significant impact or where we're starting to learn more?
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So that's a great question. And a lot of that conference, this conference is actually based on that, because what is happening is people are living for longer, longer lifespans with this disease. And so what is happening is slowly and slowly we're discovering new effects of the disease that were not apparent. You know, maybe 20, 30, 40 years back, for example, there was a talk about people having problems with speaking. And that's the reason for that is because there's a problem called myopathy, which means the muscles, they don't function fully properly because of the disease because crystals also go into the muscles. And so, yeah, so that muscular effect leaves because there are muscles all over the body. So the effect on the muscles then affect other things like for example, voice. People are also concerned about crystals in the brain.
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That doesn't sound good.
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Right. Whereas there's really no clear evidence right now. We don't know yet how many crystals are there, what their effects are. But slowly and slowly those things are coming out. Also there are issues about people having the ability to have children because of the crystals. So yes, there are essentially many other problems and that's why it's called a systemic disease. And it's also very challenging because then the patients, or actually the parents of the patients, the kids, they don't really sometimes know which doctors to take them to. So usually it's a nephrologist that handle these. So because they handle the kidneys and I said kidney is the major problem, major disease that get, sorry, tissue that gets affected. But eventually they have to see all kinds of doctors because they have to see an ophthalmologist, they have to see a nephrologist. If you have muscle problem, you have to see muscle specialists. So it becomes challenging to be able to have the need to see so many different doctors and also you have to see specialists because not every ophthalmologist knows about the disease, not every nephrologist knows about the disease. So there are only a few selected patients that you can go to. And that's where the organizations like Cystinosis Ireland become very, very important because they help bring the families together into the conferences. They help create research infrastructure for researchers to do new research, also for researchers to present their work. And also assisted nurses island is very helpful to the families to direct them to the right people who can actually help them. So yeah, they do such a fantastic job in really helping the families.
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Yeah, it sounds like this conference is really important given that this is an orphan disease and so few people have it in each individual country to come together, to not feel alone, I imagine, for the patients and the families. But then share this best intelligence, the latest research so that people can get the right help, the right treatments, the right doctors.
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Yeah, exactly. Another great thing about this is actually brings also researchers and families together. So there's a scientific session and there are family sessions. And so it gives opportunities for families and the researchers and the doctors to get together which is actually great for everybody because researchers benefit from that because there's nothing more motivational than to actually listen to the stories of the patients because that just really gets you excited about trying to solve these problems. It's also good for the families to learn from the people who are doing the real research and also from the doctors to get the best possible advice. So yeah, it's just a wonderful gathering and everybody is just very, very friendly. Everybody is after the same thing which is to solve the problems and help people.
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Well, Anuj, thank you for coming in to us and best of luck with your research.
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Thank you so much. Thank you for the opportunity. It was awesome.
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As I mentioned, Professor Chauhan is in Dublin speaking at a major international conference on cystinosis being organized by Cystinosis Network Europe and hosted by Cystinosis Ireland. For more information on the disease visit www.cystinosis.ie Future Proof Extra with Jonathan McRae proudly supported by Research Ireland on new news talk.