A conversation with Sara Riordan, MS, CGC, and the first patient to receive the CRISPR-based therapy for sickle cell disease
Sara
Victoria I am so excited to be speaking with you today. First off, I would like to ask how you are doing?
Victoria
I’m doing great!
Sara
I am excited you are here to tell us your story and your experience with sickle cell disease and participating in the clinical trial for CRISPR therapy. Could you walk us through what it was like growing up with sickle cell anemia?
Victoria
Growing up, it was a challenge. I received my diagnosis at the age of three months, and also had my first crisis at that age. So it made my entire childhood very challenging. My earliest memory of a pain crisis was pre-kindergarten at about four years old. I was at school all day having fun and I was excited to go home so I could play outside with my best friend. But the pain started as I was changing my clothes and it was like lightning. It hit me first in one of my arms, moved across my chest, down into my other arm and within minutes my entire body was just covered in pain. That was just my first experience, but one that I would experience time and time again throughout my entire life into adulthood. Which meant for me, long hospital stays, IV and oral pain medicines, blood transfusions and so many limitations. And some of those limitations were dream crushers.
My first dream was that I wanted to cheer. My doctor said that was too much exertion and would send me into a crisis. In high school I wanted to be a basketball player. I had the height and my family enjoyed basketball, so I wanted to get out there and try it. But my doctor said again that it was too much exertion and would for sure send me into crisis. As I moved into adulthood, I wanted to be a doctor, but with the class load, my doctor advised against it. Dream after dream was crushed. I started a nursing program, but it sent me into a three month crisis that took away my ability to use my arms and legs. I couldn’t feed or bathe myself, and that crushed that dream for me.
Sara
Wow, I can’t even imagine. And you have kids, and sometimes during these hospitalizations, your kids would be at home?
Victoria
Yes. Some of my crises happened in the middle of the night. So I could have a day with my kids, put them to bed, and then I would have to get whisked away by ambulance or my husband would carry me to the ER. So my kids would wake up without me there and have to leave and go to either my momma’s house or my mother-in-law’s house or a friend of the family. This happened time and time again, and brought fear and changes in their behavior. I didn’t realize it at first, but it got to the point where my son’s teacher called me to the school and said, “I’m just gonna be honest Victoria, Jamarius is acting out because he’s afraid you’re gonna die. He’s trying to get kicked out of school so he can be home to watch you full time because he’s afraid that you might pass away while he’s at school.”
That was my wake up call to reignite my fight. I was at my point of giving up, but when I saw how my struggle instilled fear in my children, I couldn’t imagine what my death would do to them. So I knew I had to fight to be here for my children, I didn’t want them to suffer.
Sara
Absolutely. How did you first learn about the CRISPR gene therapy trial and what ultimately led you to decide to participate?
Victoria
The first thing I heard about was the haplo transplant that a woman from Chicago had done. It gave me a little hope. I was in the hospital with another pain crisis at that time and was given Dilaudid and Ketamine with no pain relief in sight. So that’s when I called all of my doctors into the room and I asked them about the haplo transplant and if they knew of anything else that could help me because I just couldn’t go on like that. I wasn’t living, I was just existing. Unfortunately they didn’t have any answers for me.
In 2018 I met Dr. Frangoulwith hopes of doing a bone marrow transplant with my brother. My biggest fear with that was Graft vs Host Disease (GVHD) and that possibility was terrifying because my brother was only a half match. I didn’t really want to exchange the devil I knew – sickle cell disease, for the devil I didn’t know – GVHD. I knew my daily medicine basket would double in size, if not triple. But I wanted to do something. During one of my testing processes in Nashville, Dr. Frangoul approached me at my bedside and introduced me to CRISPR. In response, I only had two questions. One, was there a chance of GVHD? His answer was no, because the cells I was getting were my own that were edited and then put back. And two, if it didn’t work, could I still move forward with the haplo transplant? The answer to that was yes. I wanted some hope, and his answers gave me that. So I said yes.
Sara
Those were super smart questions to ask. You’re very lucky that you found Dr. Frangoul, but it took a lot of advocacy on your part to ask your doctors for possible treatments.
Victoria
Yeah, because I was at my breaking point. I had to ask for something because I was just tired of the cycle of coming home, being OK for a week, sometimes a month or months if I was lucky, and then having another crisis.
I could be anywhere, in the grocery store or out and about, and then I’m back in the hospital for a week or month or longer. Being taken away from my husband and kids and not able to be a part of their lives and their activities because of my crisis.
Sara
So what was it like? You decided to go into the trial and you were the first enrolled participant. What was it like participating in the trial and receiving this really novel therapy?
Victoria
It wasn’t an easy experience, but it was refreshing to be in the hospital by choice for the first time. So I looked at it as my time. I was fighting the disease that had been attacking me my whole life, and I was blessed to have the team that I had. It was uplifting and I didn’t feel like I was in the fight alone. They listened to me and I listened to them. And one thing that was different about this hospital stay is that they treated my mind by including a therapist. It made the experience easier. The conditioning and collection phase was fine. I was on a machine for six hours a day for three days straight to collect my cells, followed by a month-long conditioning phase, which included chemotherapy. About two weeks after I received my new cells – July 2, 2019 – I lost my hair. I kind of laughed if off. I sent my kids pictures and they said, “Hey, you look like Papa now!” But the mouth sores from the mucositis were terrible. That was the hardest part for me. When even my saliva felt like glass going down. But it was short lived, and then I began to recover. I began to regain my strength. I was able to do things that I hadn’t done in a while on my own, like getting in and out of the bathtub without assistance. I was able to walk around the halls. They were small changes at first, but receiving the cells was very emotional for me, even though nothing changed in the moment. I cried tears of joy because I knew that my life was changing. Even though I was the first, I had faith and I knew God didn’t take me through all of this for nothing, and I was surrounded by good people, so I knew the outcome would be good.
Sara
I’m so glad the trial provided you with so much support. When did you have the realization that this really worked and was going to change your life?
Victoria
That realization honestly didn’t happen until about April of 2020. I began to taper off of my medications. Everything began well, but because of the COVID shut down, my pharmacist had trouble getting the fentanyl patch to do the taper. I had made it down to 50 and then I couldn’t get the rest. So I went through that pretty much cold turkey and that set me back as it caused extra body aches when I was agitated. And then on top of it, my husband was deployed to Washington DC and I had three children at home. We were navigating virtual learning and the world was on fire, and the George Floyd situation was happening at the same time. So it was heavy.
But one morning I woke up after the withdrawal and everything was done. And the room seemed brighter. I didn’t feel anything. My immediate reaction and first thought was, am I dead? I had to pinch my face. I pinched my thighs and I was like, “Oh, I can feel that. But I needed more reassurance.” So I called all of my children into the room and they ran in and when I saw them and realized they saw me and heard me, I gave them hugs. I realized, this has worked. I’m better. I don’t feel pain. My breath is clear. I don’t have any restrictions. I could take a deep breath without feeling tightness. My joints didn’t ache. I wasn’t stiff. I thought, this is what normal feels like. I was so grateful and I thanked God in that moment and I cried. This is what I missed out on for so many years. I challenged myself day after day with different activities, like jumping on the trampoline with my children. We couldn’t really go anywhere because of COVID, but I could run in the yard and keep up with my children. It was unbelievable.
Sara
You were feeling what normal should feel like for the first time.
Victoria
Yes. And I was so grateful for it.
Sara
How has your life changed now that you have a new normal?
Victoria
My life has changed tremendously. I’m able to attend my children’s football games, go to my daughter’s parades in the winter time. I work full time. Before, I was completely housebound with help from a PCA. It was emotional to call her and tell her I’m better now and can do it on my own. So everything has changed. I get to be a patient advocate now and speak for other sickle cell patients and guide them through this journey. So life is good.
Sara
That’s amazing. Why did you decide to take on the patient advocate role and what does it mean to you to do that work?
Victoria
I decided to take on patient advocacy because I feel it’s important. When I was dealing with sickle cell disease I often felt alone and voiceless. It felt like what I wanted or needed was not important to anyone else besides me, so it made my journey even harder. So if I could be that voice for other people it means so much to me because I know what it means to them.
Sara
I think that’s so important to hear from someone who’s been through it before and has similar experiences. When you’re talking to patients with sickle cell disease about gene therapy and your experience in the clinical trial, what are some of their biggest fears about gene therapy and what do you tell them?
Victoria
One fear is not about the therapy itself, but about the place where they would receive the therapy, because most sickle cell patients struggle with being believed when they go into the hospital. They want to know if the person that’s going to be administering the therapy will listen to them if they say hey, something feels off. So they want to know about the care team and accessibility because of the price tag. Will they have access to it because it is approved now? That is one of the biggest fears now.
Sara
When you tap into your experiences while talking to them, does that help?
Victoria
Yes it does. To know that they have choices. It helps them feel like there are people out there who care about sickle cell patients and understand. They ask if the treatment is worse than a sickle cell pain crisis and I tell them it isn’t as limiting or debilitating as a crisis and that gives them reassurance. I tell them it’s not easy but life with sickle cell disease isn’t easy.
Sara
I imagine that the equation is different for everyone, right? Because everyone experiences the disease differently. And so for you, it was so debilitating, it was an easier decision for you to join the trial. But everyone is going to have different factors to consider.
Victoria
Yes, but I think we all share knowledge of what sickle cell is capable of doing and how quick it can change because we all know someone with a completely different experience. Someone may not experience that much pain but because of the disease, can suddenly have a stroke, heart attack or pulmonary embolism. So it’s treating more than just the pain element of sickle cell disease. There’s a lot more to it than just pain.
Sara
Absolutely. I really admire your work as a patient advocate. I think that’s incredibly important. What can healthcare providers and members of the care team do to better help patients access clinical trials and treatments for sickle cell disease?
Victoria
Stay informed and share with us. Share where we can access those trials and the qualifications that we may need, as well as resources for funding to help us get to the trials. It is the worst feeling for a patient to be in crisis and seeking help from a care provider, and they don’t have any answers for you.
Sara
So we should stay informed not only about the trials and therapies, but also about resources that we can help patients with.
Victoria
Yes.
Sara
At Genome Medical we’re a telemedicine genetics services provider and we have a very large team of genetic counselors and our genetic counselors talk to many patients every day that have a rare disease or rare genetic condition. I would love to hear from you how we, as genetic counselors, can better help patients and families understand if gene therapy is right for them?
Victoria
Well. I think you can have your patients write down a list of things that they deal with and go over some of the benefits of gene therapy and what the capabilities are because a lot of people wonder if it is right for them. If the patient doesn’t feel pressured but just has the knowledge then they can weigh their choices. If they have the gene therapy knowledge, they can take some time to think about it. Because most warriors need to pray about things first, like I did before making the decision. So information and patience.
Sara
That’s very helpful. Providing information and options and then having patience. It’s a different journey for everyone.
Victoria
Yes. And I think it’s important to be available when your patients have questions. What I admired about my doctor is that I could send an email when I had a question and I’d get a response. So they made me feel really cared for.
Sara
I just have to say, I love seeing your face when I open up LinkedIn and there’s new articles about the work you’re doing to raise awareness about gene therapy. In your experience with CRISPR therapy, one of the phrases you use is “super cells.” Can you tell us about your super cells and how you talk about them when you’re doing your patient advocacy work?
Victoria
I explain to everyone that they are now called my super cells because they were once sickle cells that caused me a lot of pain, discomfort and misery. Now they’re the cells that I need to breathe, move freely and enjoy this life. So they were edited from sickle cells to super cells. And that’s what I just love to call my edited cells because they are doing a super thing for me.
Sara
From sickle cells to super cells. I love that! I have one more question for you Victoria. June 19 is World Sickle Cell Day. As you reflect on the progress that has been made recently, we now have two gene therapy approvals for sickle cell disease, what are your visions for the future? What do you hope to see 10 years from now, on World Sickle Cell Day?
Victoria
I would hope to see one day that this treatment can be done without the chemotherapy portion. That would be awesome and not just with gene editing. I would like to see advances in medications for sickle cell patients who may have had strokes or pulmonary embolisms. I would like to see these patients have an equally enjoyable life without having to go through the treatment. I want everyone to be included. So that’s what I would like to see within the next 10 years on World Sickle Cell Day.
