Podcast - Battling Cystinosis: Perspectives from a Doctor and a Patient Turned Advocate

Shawna Watley: Welcome everyone, to the Holland & Knight Public Policy & Regulatory Group Podcast Eyes on Washington in partnership with the Rare Disease Diversity Coalition (RDDC) and Black Women's Health Imperative. Today's discussion will be about genetic kidney disease. We would like to extend a special thank you to Vertex Pharmaceuticals and Travere Therapeutics for their sponsorship of this discussion. Joining us today is Deanna Darlington, former interim director of the Rare Disease Diversity Coalition and now a consultant, as well as Sara Healy, cystinosis rare disease patient, and Dr. Agnes Costello, consultant and volunteer for NephCure Kidney International and Asian Women for Health. First, I'd like to ask Deanna, can you talk to us a little bit about the Rare Disease Diversity Coalition, the work that you all have been doing and why it's important for you all to be a part of these types of discussions.

Deanna Darlington: I'd love to share more about Rare Disease Diversity Coalition. We're a multi-stakeholder coalition, we are under the umbrella of the Black Women's Health Imperative. We are a little over two years old now, and the whole impetus and sort of birth of RDDC came about when a number of multi-stakeholders reached out to our President and CEO, Linda Goler Blount, MPH, of the Black Women's Health Imperative. We really wanted to have an organization that focused on diverse communities within the rare disease space, recognizing the extraordinary history and work that the Black Women's Health Imperative has conducted over a number of years. We have a very diverse steering committee that we report under, and then also we are separated into five different work groups. Those work groups came about after a number of discussions over an extended period of time where we brought in thought leaders to really help guide us and help us understand sort of what are the barriers and challenges. So we brought in researchers, we brought in health equity organizations, we brought in rare disease groups, to really have a clear understanding of those challenges and barriers that impact rare patients and diverse communities. Out of that, we came out with five work groups that really represent the key challenges we have in this space. The first work group is Diversity in Clinical Trials. We all know that is a significant issue from a health equity standpoint and that we face as a country right now. Also, we have a Provider Education work group to address some of the challenges that we have from providers' education, not only on rare disease, which is pretty robust, but also from a health equity standpoint. We also have a Patient and Caregiver work group, and that work group really examines the gaps that rare patients in diverse communities face and try to develop evidence-based solutions to support that. We also look internally at patient advocacy organizations and try to help them understand appropriate tools for reaching out or even understand how they're currently reaching out to diverse communities and what are their Diversity, Equity and Inclusion (DE&I) efforts internally. We also have a Policy workgroup in which we have signature legislation for RDDC, in which we try to encourage more diverse healthcare professionals to work in the rare disease space, but also to encourage diverse healthcare professionals and healthcare students to really look at this as a career. Finally, we have our Delay in Diagnosis work group. We all know that's a huge challenge barrier as pertains to the rare disease community, as well as a diverse community. We really tried to structure our organization in such a way in that we develop key work groups to address the many challenges that both the rare disease community face, as well as those diverse communities. When you step back from the issue, you really recognize that having a rare disease is very similar to the health disparities that we experience in our healthcare system. We're really proud of the diversity of our stakeholders, our commitment to produce evidence-based solutions to help address these issues and our target focus on inequities in the current healthcare system that has impacted traditionally marginalized communities of color.

Shawna Watley: Thank you for explaining to us the amazing work that you all are doing at RDDC. I would like to start off with Sarah. Can you talk to us as a patient about cystinosis and your experience? Thank you so much for being with us today.

Sara Healy: Cystinosis is a lysosomal storage disorder, and it's ultra-rare. Only about 500 people in the U.S. have it, and a little over 2,000 people in the world have it. You can imagine how difficult it is to find a doctor who knows about it. I think there's maybe three that I know of that are experts in it.  I think one of them is a pediatrician doctor. It has been difficult, but I think luck was on our side when we were little because we grew up in a small town in North Dakota and they didn't really know anything about what we had. We started developing symptoms a little before we were 12 months old. After mom and dad had us — I say "us" because I have a twin sister, Jana, who also has cystinosis — first they thought it was vitamin D deficiency. Then they thought my mom and dad were neglecting us, and then they thought it was rickets. When they couldn't figure it out, they sent us to the University of Minnesota because they deal with rare conditions or conditions no one has really heard of. They thought it'd be best if we went there to be seen. Jana at that point was too sick to be tested on, so they tested on me and they found out what we had was cystinosis, and my parents, who are from a small town, were like, what? Luckily, Mom took the lead because she was a lab technician in college. She knew all about the different types of labs and what they mean, and she knew the right questions to ask. She was very aggressive about what she thinks that we needed and she wanted to be involved in the process. Dad was more like the comedic relief and give us some relief from all the testing and procedures we had to go through at such a young age. Luckily, an attendant took interest in us. Once they figured out what we had, he found out there was a clinical trial for drugs that supposedly help treat cystinosis. At that time the drug was still in the clinical trials and they didn't really have any way to treat us. We were lucky enough for the doctor, I guess, in the clinical trials to get the medication and the people who were in the clinical trials got to stay on the medication. And I think they didn't approve the drug until the '90s, and we were born in '83, so we were lucky enough to get into the clinical trials so we could get the medicine right away. Unfortunately, Mom and Dad had to deal with our tantrums of not wanting to take the drugs because it tasted disgusting. You can imagine how hard it was for our parents to try and get us to take this liquid medicine that was disgusting and we didn't want to take it, but it was the only thing that was helping us.

What is Cystinosis?

Shawna Watley: Can you tell us exactly what cystinosis is and why is it a genetic disease?

Sara Healy: Both parents have to have the recessive gene in order for the kid to get it, and it's also a one in five chance that their kid could have it. It's more likely that they'd become a carrier than actually get it. When my mom first wanted to have kids, the doctor told her she couldn't have kids, so they adopted our first sister. After that, they found out that she could get pregnant, so she had, I think, like every two years or so, a kid. There's seven of us total. Jana and I were the youngest and we were the ones to get it. I'm a part of the Cystinosis Research Network, and they describe it best. It's a rare genetic metabolic lysosomal discharge disorder caused by a mutation in the CTNS gene on the chromosome 17P13, which results in an abnormal accumulation of the amino acid cysteine in various organs and tissues throughout the body. Basically the first thing it affects is our kidneys. These crystals that form inside the amino acid have nowhere to go. So they basically push their way out of the amino acid. By the time they have formed crystals, those crystals attack the organs in our bodies. With treatment, it keeps it in check and keeps it from attacking any other organs. Unfortunately, most of the time when they catch it, it already does some damage to the kidneys because it's the first thing to go, and then it affects the eyes. Cysteine crystals can build up in your eyes, and you can become blind without treatment. We also have treatment for that. It's specialty eye drops that you put in every day, and they are really expensive. You put it in every day, and it helps keep the cysteine crystals at bay so you can have better eyesight. With treatment it only really affects the kidneys if you continue to take the medication. Before the treatment, it would start at the kidney and then it would go to the eyes and then it would go to muscle wasting, which affects swallowing and walking and having the strength to open to something as simple as a jar. It's a pretty extensive rare genetic condition, and a lot of our conditions don't have medication or treatment or clinical trials to even help them treat their disease and live a semi-normal life.

 It's a rare genetic metabolic lysosomal discharge disorder caused by a mutation in the CTNS gene on the chromosome 17P13, which results in an abnormal accumulation of the amino acid cysteine in various organs and tissues throughout the body. Basically the first thing it affects is our kidneys.

Shawna Watley: I really appreciate you being willing to open up and share for others to learn. I wanted to talk to Dr. Costello a little bit about her and her sister's experience and her family's, quite frankly, experience with this. Are there tests that are being administered to infants to catch this type of rare disease? If you could just talk to us a little bit about that.

Dr. Agnes Lo Costello: When I think about Sara's journey, it's similar to a lot of patients that I've come across with rare disease. Traditionally, if we focus on kidney disease, a lot of times patients won't see a physician until they have symptoms. The physician will then look at blood levels, urine, and they look for crystals as well. Then it's really with a thorough clinical examination, sometimes the physician will suspect something and order additional tests such as an ultrasound. If they are still not sure, they may consider doing a procedure where they do a kidney biopsy, where they take a very tiny sample of the tissue and examine it in the microscope. Despite all that, a lot of times the cause of the disease is unknown. You have a disease, especially rare disease, where it affects not just the kidney but other manifestation and makes it very complicated and challenging. I think more of a comprehensive approach would be factoring in family history and tracking all the various multi-system manifestation of that clinical presentation. Then there's a push for genetic testing. Genetic testing has gone through such a revolution in terms of the ease of the test and the amount of different genes that we know associated with disease, I think that has shifted a little bit as well. There's also a lot of other challenges, but typically when I think about rare diseases, it's really diagnosing. Sara's mother was pushing and being aggressive. I think being your own voice and doing research and working with your physician and finding that partnership will really help. Also, never ever be afraid to look at genetic testing as a as a way to help solve the puzzle, so to speak.

Shawna Watley: Can you speak to us a little bit about who determines whether patients should receive genetic tests?

Dr. Agnes Lo Costello: When you think about genetic testing, there's different ways of thinking about it. You have the newborn screening where for certain disease is now part of a panel for newborn screening. For someone that is a little bit later when they start having symptoms. I see it as more of a partnership with a physician to kind of push for that genetic testing. You can look at a panel of many different genes, but you have to have something that you want to hone in on. In this case, we talked about kidney disease. If there's a kidney dysfunction, I think it's really important to partner with your physician to kind of say, you know, my family history is as such and it's been shown in a lot of literature that 25 percent of patients with family history of kidney disease have a genetic kidney disease. Recently a panel met, and they talk about who should get genetic testing. I think from a physician perspective, there's been the push for can we set up proper guidelines so that we can get these patients screened sooner. On top of the list is really a positive family history of kidney disease, early age of onset of kidney disease, like in Sara's case. They experience symptoms really early and want to catch that early, especially if there's other organs affected as well. Then we should start, you know, bringing genetic testing sooner rather than later. Also a lot of times it's really working with your doctor to highlight some of the things that I find. Patients sometimes are reluctant to speak up for themselves. Something that may be trivial could be a trigger for something that is a sign of a possible genetic disease.

Genetic Testing Barriers for Diverse Communities

Shawna Watley: Do you find that there are some barriers for diverse communities as it relates to genetic testing? And if so, can you speak to that?

Dr. Agnes Lo Costello: We can spend hours talking about the barriers that I think are definitely there. It could be socioeconomic status, but to me it's more awareness. I think a lot of patients are not aware that genetic testing is available. If they're not aware that genetics play an important role and family history plays an important role, then they're not even going to consider genetic testing. Culture may also be a factor. In my culture, the Asian culture, there's a stigma of "I don't want to share my family history or talk about inheritable diseases" because it affects reproduction. There is also that cultural stigma of not wanting to seek genetic testing. The other barriers I think are obvious. Access, especially for communities of color, and some of the other communities where they're just not even getting the typical preventative care that they would need. How would you consider even talking about genetic testing when you know there's relatively limited access to preventative care? I think definitely access is an issue. Even If you have access a lot of times with insurance coverage, I think there's still something that a lot of groups are working on to ensure that we do have access to genetic testing for these patients.

 The other barriers I think are obvious. Access, especially for communities of color, and some of the other communities where they're just not even getting the typical preventative care that they would need.

Shawna Watley: You talked about education and really educating communities and working with different community stakeholders so that individuals who may not have access are learning about their options and things that they can utilize to make sure that their health is being addressed appropriately. So thank you for the work that you're doing. I wanted to turn it over to Deanna because I know she had a few questions for you all as well.

Genetic Testing Challenges

Deanna Darlington: Sure. Thank you, Shawna. So again, I'd like to just thank our guests and welcome that. I'm very excited to have both of you here. Dr. Costello, I'm going to jump over to you. What are the challenges to getting tested, and are there opportunities to support better testing?

Dr. Agnes Lo Costello: I feel like when we talk about general testing, sometimes a lot of patients, especially in our communities, we don't look at preventative care in the typical way. We only see care when there's symptoms. There's often a delay in diagnosis in that regards. It would be ideal to have routine screening, like when you'd bring your kids to the pediatrician and they would do the typical screenings, typically just the occasional blood test and a urine analysis. A very typical traditional panel of health tests, if you want to call them that, just to identify any abnormalities or any things that need to be followed up. I think there is definitely a lack of preventative care and screening for kidney disease or any general health in the community. So that's one aspect of the limitation. In terms of genetic testing, I think that's another layer of that. There's limited ways, especially in the diversity community, for screening. Typically, people would not screen for genetic disease unless it's a cause. So without the appropriate testing for preventative care, to identify a signal, that would be hard to generate a need for genetic testing.

Deanna Darlington: I know I've heard you speak on a urine test, and I know that can be just very simple. Is that something that we think that's a challenge as well?

Dr. Agnes Lo Costello: When I was in practice, it was always easier to ask someone to pee in a cup versus taking a piece of tissue or blood sample. I think urine analysis is very easy. Not only does it pick up kidney disease, it can pick up diabetes and a lot of other things. To use an analogy, if you go to CVS, you can get your blood pressure check. Can we go to a community center and just do a simple urine analysis to get an early understanding of how your kidney health is functioning? So I'm really thinking there are noninvasive ways to assess your kidney health, and we should be pushing for that more for that as an initial screen.

Deanna Darlington: Is there a problem with reimbursement? I know that with genetic testing, maybe not, but even just something as simple as a urine analysis. Are there barriers from a payer standpoint?

Dr. Agnes Lo Costello: So typically, I think from most payers' perspective, a urine analysis, it's reimbursable. It's not expensive. Even if it's out of pocket, it's not an expensive test, and it shouldn't be. Genetic testing can be expensive, but if your physician is an advocate for you and you push for it and there's a clear clinical rationale for doing genetic testing, a lot of times the payers recover genetic testing. There's specific clinical trials looking at unique genetic kidney disease that will also offer genetic testing. I think that's another avenue of getting that coverage, is participation of clinical trials. There's also other companies out there. They're running genetic testing specifically for kidney disease, and there are good resources where they can explain the process, have genetic counseling and then they work with your insurance to get coverage. I think there's definitely barriers in terms of reimbursement, but I think there are ways to circumvent that. In my mind, the most direct route is really working with your physician and pushing for it and make sure that there's a clinical rationale to cover the genetic testing. Because you do need to get to the bottom of what is causing your kidney disease and not just what's causing it, but what are the treatments that's more effective for you. I think to me, that's another rationale as well, because we know certain genetic tests, certain kidney disease, will not respond to immunosuppressants. So why am I subjecting my patients to high-dose corticosteroids for a long time? If I do a genetic testing, I know exactly what it is and what are the right therapies so I can minimize the patient's exposure to not effective medicine.

 I think there's definitely barriers in terms of reimbursement, but I think there are ways to circumvent that. In my mind, the most direct route is really working with your physician and pushing for it and make sure that there's a clinical rationale to cover the genetic testing.

Deanna Darlington: Thank you so much for that. Sara, I'm going to come back to you. The doctors tested you when you all were originally diagnosed. I'm assuming from a general standpoint that there's still general urinalysis or general testing that's involved to treat your disease.

Sara Healy: None of our family members really got tested to see if they had the gene or the recessive gene or anything like that. I'm assuming it's because they didn't want to know. As far as the other types of testing we see, we see an overall allergist in at the University of Michigan where we got diagnosed every six months. She also has some knowledge of cystinosis, so whatever she doesn't understand, she's in contact with experts in cystinosis, which are, usually the one she's in contact with is in San Diego. They always check our blood every three months, they check the CBC panel, our GFR, make sure everything's going good with our kidneys. I didn't personally have to have a kidney transplant until I was 33, and I'm 39 now. Jana had a kidney transplant four years before me, so we were lucky enough to find donors. I mean, she didn't have to do dialysis, but I had to do dialysis for a few months, which was a whole other challenge in itself. Because we have a rare condition, they all want to follow the general guidelines on how much they're supposed to take off and dry weight. I take like 40 pills a day, and you can't restrict me on fluid if I'm trying to swallow all those pills. The doctors never really listened to me until it was too late, and I had built up too much fluid. Then they had to postpone my kidney transplant until they got all the fluid off and my heart was better and it just became this old debacle. We have a regular general practitioner, and then we have a nephrologist, and sometimes we see other doctors. When I had a throat issue, I saw an ear, nose and throat doctor and a speech therapist, and you know, things will arise, but our two main ones are our general practitioner and our nephrologist.

Deanna Darlington: Thank you for sharing that. I appreciate that. Did your sister have a kidney transplant? I think that you just said that she had one as well.

Sara Healy: Yes, she had one, and they transplanted her first and left her two kidneys in. But she had complications because her two kidneys weren't helping her because at this point they just kept dumping. They weren't filtering anything out. Because they weren't completely shutting off, her new kidney went to sleep. Then she had to have a second surgery to get the kidneys out so her new kidney would wake back up so she wouldn't have to lose a kidney. She just got this. 

Cystinosis Research Network

Deanna Darlington: I just applaud you. I mean, you're so engaged and educated on your disease. I'm not quite sure of the work that you do at the Cystinosis Research Network. Did you all start that organization?

Sara Healy: Jana and I became a part of Cystinosis Research Network when we first discovered them, because we lived in a small town, no one knew about cystinosis, we kind of felt secluded because they didn't understand the side effects. They thought we were different, and they didn't really understand us. Once we went to college, we wanted to kind of find more people like us because we knew there was somebody else like us. We just we didn't know where to look. We looked on the Internet, and we found a group called Cystinosis Research Network and we saw that they held conferences like every two years. They had a conference where all the families and adults and kids and teens would meet up and they'd have expert doctors there talking about clinical trials and new testing. They were trying to see if it would work or if there were any further advancements. We went there, and we saw what they were doing. Later on, they said they wanted to start an adult group under them to try and get the adult voices heard because they have different problems from the child and teen perspective. They weren't sure what those problems were or how to reach out to the adult community, so they created an adult group under them called the Adult Leadership Advisory Board. Jana and I became board members of that, and we have other people in our group like Brian, Karen, Allison, Christine and a couple of others. We try and communicate the problems adults have, and we try and reach out to them and see if they want to talk about it on a podcast to try and get our voice more heard. When cystinosis was first discovered, they didn't really have a treatment at all. Basically you could get a kidney transplant, but then they didn't expect you to live much longer. Once the treatments were available, people started living longer, and they were trying to figure out the new problems. Like the problem of us trying to find a doctor who's willing to take on our rare disease so we don't have to travel like thousands of miles just to see someone who knows what we're going through.

Rare Disease: An Uphill Battle

Deanna Darlington: That's great. Thank you so much for sharing that. Dr. Costello, it occurred to me it must be a challenge for doctors to be educated on such a rare disease. How do we ensure that medical students, residents and young physicians are more aware of these rare diseases? We all know this leads to not having that diagnosis and that delaying diagnosis is just so often a huge barrier for rare disease patients, and I would say compounded for those rare patients in diverse communities.

Dr. Agnes Lo Costello: Being a transplant clinical pharmacist in practice for a long time, I just see a lot of kidney transplant patients with either unknown cause or rare disease. I think I shared with a different forum about a patient with hypoxia. The disease course is similar to what Sara experiences with cystinosis. The accumulation of oxalate in the kidney, in the eyes, in the bones, etc. I have to be very honest, it was the first rare disease our team had seen. The whole team admits that we didn't manage the patient as well as we should have because we didn't know how best to manage the fluid, how best to manage the kidney and the mobilization of the oxalate to prevent additional damage. The patients end up needing a second kidney transplant, and the patient's doing well, but it was it was already delayed and he did have other clinical manifestations. Having had that experience as a clinician working side-by-side with the physicians, we are frustrated because rare disease is rare and it takes a compassionate surgeons, physicians and the whole team to really care for the patient and listen. I think we need to start from the ground up, not even just thinking about rare disease, but part of the physician training and any clinician training. I don't want to just harp at physicians because I think all healthcare providers have to be compassionate and listen. I think that's what it means to be a good healthcare provider so that we can diagnose the disease and manage it better. The other aspect is that we need to leverage some of these experts that are known in this rare disease and allow them to discuss it with the community so that the community is not afraid of these rare disease. It's all about education and sharing resources. We do have this center of excellence that maybe focuses on certain rare disease. I think it's for them to train and demystify these rare disease. In the end, it's about the patient. There are resources that the community physicians should go to. It's really a partnership. I look at it as different ways of listening to the patient. Also, we need to identify mentors in these rare disease so that the community can refer to them and be partners with them. The more we learn, the more we share, the better.

 Having had that experience as a clinician working side-by-side with the physicians, we are frustrated because rare disease is rare and it takes a compassionate surgeons, physicians and the whole team to really care for the patient and listen.

Deanna Darlington: We talked a little bit about the centers of excellence and engaging with community healthcare professionals. I'm curious if you could share some insight with us as to how can we be better stewards for communities and engaging with the African-American community, the Asian-American community, the Latino community, the transgender community, all these different communities. How can we be better stewards in that regard as well?

Dr. Agnes Lo Costello: I think there's many organizations addressing this. Health literacy empowered these patients to better understand health. We use big words and big languages. I think patients are sometimes afraid to have these difficult conversations. I think it's about the ground up, if I can. We somehow, at an early level in anybody's exposure to education, is empower them to have the knowledge and the ability to have good conversations with the physicians. I think you and I have a conversation previously and I said, you know, sometimes I feel like even for me when I go to a doctor's office, I forgot, what am I supposed to say to the doctor? I see the doctor. I get nervous. I'm like, oh, my goodness, what is he saying, what she's saying? I only register like 5 percent or 10 percent. I think it's important just to be prepared when you visit a physician. Kind of empower the layperson — I'm just going to call a layperson because it can be anybody — to have the confidence to ask the right questions. It may be a small question, but like we discussed earlier, a small question could actually be very important. It's really the fundamentals of health literacy and empowering the patients to have the confidence to have that conversation with a physician or a health care provider.

Deanna Darlington: I think also having a cure partner with you as well could take some of the anxiety off of the patient. They're going through enough already. But thank you so much. You are always so insightful to me, and I always appreciate our dialog. Sara, thank you so much for all the work that you've done to really educate others about that disease. I appreciate that. So I'm going to pass it back to you, Shawna. I don't know if you have any additional questions.

Shawna Watley: Thank you, Deanna, thank you, Dr. Costello, and thank you, Sara. Sara, your journey and the strength that you have shown is so inspiring. The number of lives that I'm certain that you have impacted just by your willingness to use different platforms to educate folks like myself on this rare disease and some of the things that we can be doing in our communities to make sure that folks are educated. Dr. Costello, the same. Really appreciate you being with us today and just helping us to have a better understanding of some of the things that we can be doing to help individuals with kidney disease as well as with just rare diseases in general. So thank you for your service and the work that you do. We thank the audience for listening in. Deanna, I don't know if you had a chance to share the different ways for folks to engage with our RDDC and Sara, you as well. If you want to share how folks can be connected to the organization that you're a part of, please, this would be a great time for you to share that.

Sara Healy: Cystinosis Research Network and ALAB or Adult Leadership Advisory Board. We are a wealth of knowledge and also help the community out. We have grants and funds to help pay for medications and financial hardships. We are always open. If anybody has any questions about our disease or something they're going through that they don't quite understand, there's always a way to reach out to us. The website is www.cystinosis.org.

Deanna Darlington: Thank you so much. We hope that you all will engage the Rare Disease Diversity Coalition in the future. We really appreciate you listening to this session. It was such a pleasure to have our wonderful moderator, Shawna Watley, but also our guest Dr. Costello and Sara, our patient who spoke so eloquently about her patient journey. If you'd like to contact us, you can please tap into us at our website at www.rarediseasediversity.org. We're also on other social media platforms such as LinkedIn, Twitter and Facebook. Once again, I'd like to thank our sponsors of this important topic today, Vertex Pharmaceuticals and Travere Therapeutics. Thank you for taking the time to listen to our discussion of rare genetic kidney disease.