Overcoming a One-in-A-Million Disease: Akiva Zablocki, President of the Hyper IgM Foundation


When Akiva Zablocki found out his infant son Idan had a one-in-a-million immune disorder, he and his wife Amanda were terribly worried, as all parents would be. But unlike most parents of children with rare diseases, Akiva could draw on the expertise in navigating the healthcare system he gathered when successfully overcoming his own rare and scary ordeal with a brain stem tumor. Thanks to that know-how, his wife’s background in healthcare law, some amazing clinicians, the couple’s tenacity, and Idan’s spirit, he is now a healthy ten-year-old enjoying summer camp. On this episode of Raise the Line, Akiva shares the remarkable details of his family’s journey with host Shiv Gaglani, and tells the story of how the Hyper IgM Foundation, which the Zablockis launched, is helping patients all over the world. Be sure to stay tuned for some heartfelt advice for current and future providers as they encounter patients and families with rare diseases.




Shiv Gaglani: Hi. I'm Shiv Gaglani. Our special focus on rare diseases continues today with a look at a one-in-a-million immune disorder called Hyper IgM Syndrome, which compromises the body's ability to produce responses to pathogens such as bacteria and viruses. Most people with the condition will die before they reach their 30s. Our guest today, Akiva Zablocki, learned all of this the hard way when his infant son, Idan, was diagnosed with X-linked Hyper IgM -- also called CD40 ligand deficiency -- in 2013.

Thanks to the love and persistence of Akiva and his wife Amanda, Idan has received multiple treatments and is now 10 years old and quite healthy. 


In order to help other patients and family members fight this rare disorder, the Zablockis founded the Hyper IgM Foundation in 2015 to improve the treatment, quality of life and the long-term outlook for children and adults living with Hyper IgM through research, support, education, and advocacy. The way I got connected to Akiva was the Hyper IgM Foundation actually posted the Osmosis video on the condition.  I reached out to him and he was very happy to give us productive feedback on the video, which we edited with him and his colleague's input. 


He's been great at connecting us to other rare disease groups, including being an original connection to the National Organization for Rare Disorders. So, Akiva, thanks so much for taking the time to be with us today.


Akiva Zablocki: Thank you. Thank you for having us.


Shiv: Now, by the time your son was born, you were pretty familiar with the healthcare space having worked as a consultant to Fortune 500 companies on their health and wellness plans. And you had earned a master's degree in public health from Columbia. What led to your interest in healthcare in the beginning?


Akiva: That's a great question. Looking at my background before I switched over to health, there was no indication that I was going to go into healthcare. Back when I was in college, I was an economics and philosophy major at Columbia. I was making plans to go work in finance in the summer before my senior year, and I had just been elected to be senior class president. I was spending the summer in Israel, traveling. And that's when I was very surprisingly diagnosed with what the doctors were calling an inoperable brain tumor in my brain stem.


So with that, my whole plan for my future kind of got thrown off track, I would say. Most patients in my situation would probably go see a couple of doctors and make a treatment plan. In my situation, the first few doctors I saw were telling me my brain tumor was in fact in my brain stem entirely and inoperable. So they were offering me some chemotherapy treatments and radiation treatments. But most of them didn't have a lot of faith that they would actually be able to get rid of my tumor and I was basically given two years to live.


And so at that point, I did what I hope everyone would do: continued seeing doctors. I probably got around thirty opinions from neuro-oncologists and neurosurgeons all around the world. I was based in New York at the time so I had access to a lot of great medical centers, but most of them were telling me the same thing I had heard before. Except for one doctor in Phoenix, Arizona who told me right off the bat, "Come down here. I'll take your tumor out. I'll give you a 95% chance that I can do it and you have a long life."


I took that information back to the doctors in New York and asked them, "Like, is this guy crazy? Does have sharper knives?" And everyone was telling me, there's always going to be somebody, a cowboy out there like that, who will offer you something but that's treating the impossible. Because again, you have to cut through your brain stem to get there and if they don't kill you, they'll leave you in a wheelchair for the rest of your life with a feeding tube.


Being 25, being young, and not having responsibilities, I was willing to then just take the risk and try to save myself. So I flew to Arizona, had my brain surgery with Dr. Robert Spencer, in Phoenix, Arizona, and he was right. He succeeded. He got the whole brain tumor out. He left me not in way worse off condition than I was already.  That was, I think, seventeen years ago this summer. So fast forward...I spent eleven days in the ICU recovering and then we had the process of learning how to walk, talk, getting back on my feet again. It was during that rehab process that I realized that my whole life plan was kind of going to be different.


I realized that after what I went through, I want to try to help other people who might be in the same situation as me become empowered and make the best decisions that they can make on their treatments. So, I came up with a lot of ideas of how I could change the oncology world, the brain tumor world, and decided to change my focus to Public Health. I went and got my Public Health degree at Columbia, and then, went on to work in that field.


Shiv: That's incredible. We're so glad you're with us today and obviously all the people and companies you helped along those last seventeen years certainly have been blessed by that surgeon and the fact that you didn't give up. We normally ask this question at the end of podcasts -- about advice you would give to current and future healthcare professionals -- but given that you were a patient with a very serious condition where a lot of physicians told you there's nothing to do, what advice would you give to new medical students, practicing nurses and doctors, et cetera about bedside manner or anything else that really helped you and stood out when you were going through that serious period of your life?


Akiva: Good question. I think from the medical side of it, is not to discount the patient as a stakeholder. When we are talking about healthcare, there's always places where they say, "Well, we're having a conference, and we're bringing all the stakeholders to the table. We have pharma, we have insurance, we have industry and we have the doctors." And the main stakeholder in health is always the patient. They should be the center. 


Maybe it's different now, but back in 2005 when people printed the internet and there were no smartphones, we'd come in a lot of times with our own research and the doctors would discount it. My family and I were doing a lot of research, and we were pulling studies -- even though we didn't have a background in understanding the studies -- we pulled studies, and we had information about the surgeon. He had published over 100 brainstem surgeries already. 


Most doctors just discounted because they know their field and it's hard for them sometimes to understand that other people might be doing something different. So, I think from that perspective, the advice is always to give the patients a little bit more benefit of the doubt with what they kind of know. And if you see a patient isn't at that point, I mean, help him understand what they should know and what they should be looking into.


Shiv: Yeah, absolutely. It's definitely a focus area of ours, on the so-called soft skills...things like shared decision-making, and how to approach those conversations and ultimately keep putting the patient at the center. It's one reason we've been attracted to the rare disease space for so long, because when you meet a parent or family member, or a rare disease patient themselves, they truly know more than the average clinician about that condition. They've taken it upon themselves to read the articles, understand it, and start foundations, as in your case. 


So, let's transition into that empowered patient or family member perspective. Tell us about your son, Idan, and how the diagnosis went, and then ultimately starting the Hyper IgM Foundation. 


Akiva: Sure. So fast forward. I was trying to figure out my next steps. I was working on a startup idea to help empower patients to make the best health care decisions when it comes to cancer diagnosis and brain tumors. My first son was born, and he was born healthy. He went through all these newborn screening tests perfectly and he was reaching all his milestones for the first six months or so, and everything looked normal. 


Around eight months, he seemed fine, but he started breathing quickly. We thought maybe he had a mild cold. We didn't notice it. My mother-in law noticed that he was starting to take a lot of breaths a minute and maybe we should go to the pediatrician, which we took him to. We went a couple of times that week, each time thinking it was just a virus, and that he was relatively healthy besides that.


As the couple of weeks went by of going back to the doctor, his oxygen level fell, he was definitely taking many, many breaths per minute, struggling really to get a good breath. At that point, they rushed us to the ER and started probing him and testing him assuming that there was some sort of pneumonia based on the X-rays, but they really didn't understand what it could be. 


The first couple of days there, he just went from having some oxygen on the nose, to a breathing mask, but then eventually they intubated him. I thought they were just intubating him to get some samples from his lungs. He ended up being intubated for two full weeks and diagnosed with pneumocystis pneumonia, which is very rare pneumonia. It's an opportunistic infection that you will not get unless you have a compromised immune system. 


So at that point, all the doctors kind of descended on us. We saw infectious disease. They tested him for HIV, obviously. He was negative. And then they started going through all the different tests for different kinds of immune deficiencies.  I had been through this myself...this boot camp of dealing with a weird diagnosis and trying to find an answer. So all of the skills that I developed during that time, and over the years in public health, kind of jumped in. 


He was in ICU for three weeks, and got put on a course of antibiotic Bactrim, which is really the only antibiotic that works for pneumocystis pneumonia. All the broad spectrum would have done nothing really for him. That's when I discovered that he had no antibodies at all, and never made any response to any of his childhood vaccines. They started giving him IVIG, which is an intravenous immunoglobulin dosage, and started some tests. 


He came back with an immune deficiency called CD 40 ligand deficiency, which is also called X-linked Hyper IgM syndrome. It's a very rare, one-in-a-million type of immune deficiency. Patients with this immune deficiency have defective T cells and cannot communicate properly with their B cells. So, they can't alert the rest of the immune system to pathogens or viruses, and they can't signal the B cells to produce an antibody response. 


So, if you get a vaccine, you don't make any response to it. During the virus, the B cells won't do anything to fight them off, and you won't produce antibodies, only some of the T cells might work. Being a one-in-a-million disease, there wasn't a lot of information out there. At the time, there was one page on the Immune Deficiency Foundation's website, which is a great organization but focuses more on the more common immune deficiencies out there. Most doctors would never have heard of Hyper IgM syndrome. Maybe it was on a pop quiz during the one immunology class they take in medical school.


So, that's when we started to get into crisis mode. Our son, being immune compromised, really couldn't be around people. We kind of like sheltered in place back in 2013 before that was even a term. Everyone coming over, we put masks on them and they change their outfits. I was wearing a mask every time I felt a scratchy throat back in 2013. We learned to be aware of germs and all of those things early on. 


And with hyper IgM syndrome, the only known possible treatment that can be a curative treatment is a bone marrow transplant. So that's what we knew we needed to do. Then the question for us was, what type of transplant and what type of chemotherapy protocol we would do. It was so similar to my situation. We started consulting dozens of centers and going around the world, around the country, trying to find the best treatment that we can. 


This is kind of leading to the foundation work that we've been doing. Along the way, we got a lot of attention from a fundraiser that we were doing at the time to raise funds to cover his treatments because the insurance company had denied IVIG treatments. They were denying also the transplant in the beginning. So we're raising funds, and that kind of got a lot of news attention. And that led to patients around the world reaching out to us saying, "Oh, we were always told we would never hear about another patient with this, and then we saw the article on the news about you." We realized that there's a community here that could be built, and we were probably situated in the best possible place to build that community.


Shiv: What a remarkable journey you guys have been through. How is he doing now? How old is he? Can you tell us a bit about that? And then obviously, I have a ton of questions about the foundation work and whatnot.


Akiva: So Idan is 10 years old now. He is doing amazing. He had a transplant back in 2013 when he was 14 months old, which, unfortunately, failed. After doing a lot of research, we chose to transplant him, even though we lived in New York, at Seattle Children's Hospital. The main reason is when you're going to do a bone marrow transplant or stem cell transplant, you need to get high-dose chemotherapy to kind of wipe out the organ that you're transplanting, which in this case, is the bone marrow. There's no way of getting all the bone marrow out of your body besides giving chemotherapy and immune suppressants. Seattle had a protocol that nobody else in the country has which is the type of chemotherapy called treosulfan, which is just as effective in wiping out the bone marrow but less toxic for the rest of the body which is why one of the reasons we chose Seattle. 


Unfortunately, his first transplant failed and it took us a few years to kind of realize that we needed to do it again because his Hyper IgM basically came back. Then he was transplanted again in 2016 right before he turned four, and it was a success. He has been living basically disease-free for the last five years.  Off all medication, off all infusions, going to school. Really, a normal life. He spent the summer at a horse camp, shoveling manure and attending to goats and animals and horses, so we're not worried about him anymore.


Shiv: That's amazing. Throughout the COVID pandemic, has it been relatively normal in your household, or were there extra precautions that you use?


Akiva: So that's a great question. At the beginning of the COVID pandemic...we had just spent several years trying to stop sanitizing our hands and stop being so neurotic about germs. Then all of a sudden, it was like a PTSD flashback to that world. We went and became probably more neurotic than other families at first. I think we're one of the few families out there that have not had COVID in the last two years. He's been vaccinated. He's unmasked now in camp. We're not worried about it. 


At first, going through a bone marrow transplant means a lot of chemotherapy and poisons in the body, so we wondered how well he would do but we were assured by his medical team that he would do just as well as any other kid his age. So we weren't concerned about him more than average, which is very different in the Hyper IgM community because they are very concerned. They are all immune compromised unless they've had a successful bone marrow transplant.


Shiv: That makes a lot of sense. So, can you talk to us a bit about the bone marrow transplant? We partner with an organization called Donor Alliance and recently had them on the podcast to talk about bone and soft tissue transplantation. One of the main takeaways from that is for our audience not only to sign up themselves, to be organ donors, but then also to have those consultations with patients as well. 


We also had people on like KX Jiang who runs Facebook's health platform, and they've done a ton of blood donor drives and other drives to raise awareness, but I haven't heard of a bone marrow drive in a while. So can you tell us about the process of getting that and how you got matched?


Akiva: Sure. So, I would say that being a bone marrow or stem cell donor is probably one of the most amazing things you could do. It doesn't take a lot on your end. Many of us get swabbed in college, or at some event that we go to, and we never think about it again. I know I was swabbed in grad school, and I never really put much thought into it until my son needed a donor. 


We were very lucky that my son's HLA typing was common enough because my wife and I have the same kind of genetic background. We're both Ashkenazi Jews from the same region in Europe, so we had a decent amount of donor options when we were choosing. They chose the best optimal donor for the first transplant and then they switched to a different donor for the second transplant. But I would say that there are a lot of patients out there that do not have that access.


Anytime there's a patient with any kind of mixed race, or even just mixed ethnic background, it'd be much harder to find a donor match. We were very fortunate. Actually, we got to meet my son's donor a couple of years after his successful transplant. We had asked to meet him because he was doing well two years post-transplant. Then the registry, which was the gift of life registry that he was found through, said, "Oh, you know what, we have a perfect thing. We're gonna have you guys meet him at our event." We went to an event in 2018, I think it was. It was a 500-person gala. They had a video about Idan's story and then we got to meet his donor Alex on stage in front of 500 people, which was a very big emotional journey for us, but it was very special. 


Alex was an amazing guy. He registered when he was in college and kind of forgot about it. When they reached out to him and said, "Hey, you could save a sick kid four-year-old that needs your bone marrow," he jumped on it right away. It was a very easy process for him because they can take out stem cells now. So you just sit in the hospital, you donate blood for six hours, and you get the blood back.  He saved her son's life, and now they kind of share a special bond and we've kept in touch with him since.


Shiv: That's incredible. We love hearing those stories and if there's any recording about that, we'd love to share that in the show notes.


Akiva: Sure. 


Shiv: So going into the foundation's work, this is a one-in-a-million type condition. There's eight billion people in the world, so really only 8,000 people have it. The criteria to be a rare condition is it affects less than 200,000 people, so this is even rarer than the average rare condition. Tell us about the Foundation. What are the types of activities you've been working on? Any kind of highlights or things you're very proud of the Foundation having accomplished since you started?


Akiva: Sure. We're what they call an ultra-rare condition. There's only probably a few Hyper IgM babies that are born every year in the U.S. We started off with a support group, just organizing families together and kind of connecting them because we realized that anytime another patient with this one-in-a-million disease was diagnosed, they were told that they would never meet another family with the disease unless it's in their family...like their cousin has it. 


Once you're working together, so much more information was being shared and empowering patients to make better decisions. That's where I realized that we could do so much more. I had an extensive background in health care, and was also sitting on a board of a National Foundation for ten years in the brain tumor world, so I kind of knew how charities work. And then my wife, Amanda is a healthcare attorney. So, we were really situated in the best possible place to start this foundation for these families. 


We were founded in 2015 with the goal of connecting families together, and also raising funds to help research and hopefully cure this disease. We help families all around the world kind of understand it when they're first diagnosed. We connect them with a patient liaison. We have a call with them. We connect them with a support group. We just really help them understand this diagnosis. Most of them are being diagnosed kind of out of the blue. Their son, like ours, would be totally healthy, and then all of a sudden get sick and get this rare diagnosis and they don't really know how to process it. 


We created a website and we put a lot of information that we simplified for our patients, kind of like you do with Osmosis.  I know that we connected because you made a great video on Hyper IgM syndrome, which we've shared with our patients, which is amazing.


We also help them connect to the best care. If they are patients in India or anywhere really that might not have the best options, we'll connect them with families. We've had families in Turkey that we've connected to, in Australia that we've connected to, because they haven't had the best option. We can connect them to an expert in the UK that they could talk to and he'll talk to their doctors and kind of make a treatment plan. We've had patients all over the world change their treatment plans based on the connections that we've made for them with experts in the field. We've also been raising research grant funding every year, giving grants to hospitals all around the world that will focus on understanding Hyper IgM better. 


The things that we're most excited about are the gene editing and gene therapy options that might come into play. We don't have a treatment now. The only thing that we have now is prophylaxis care, which is IVIG treatment, and our patients could stay on that for life but the median age is still twenty-four, unfortunately, so most do not make it past that third decade of life. 


If they have a match and they're healthy enough, they might have a bone marrow transplant, but the survival of the bone marrow transplant is also not amazing. I mean, you're rolling the dice. There is a 10% to 50% mortality rate with any transplant. Besides that, the success rates aren't always that amazing. So the treatment options with gene editing would be amazing. There's a couple of centers around the world that have been working on this, and we've been helping fund both fund them and also get them patient volunteers to be part of their research.


Shiv: Actually, that's exactly how we got connected. I was following where Osmosis videos were being shared, and I noticed a lot of traffic from The Hyper IgM Foundation Facebook page. I reached out to you because we had just started working with rare disease foundations like the Alpha-1 Antitrypsin Deficiency Foundation. You were very generous to give us a lot of feedback on the video and we improved the video. Then you were very generous with your network. You reconnected me to the National Organization for Rare Disorders -- who I'd met first at a conference, but you knew them very personally -- as well as other foundations. So, we appreciate the role you've played in helping Osmosis get more into the rare disease space. 


So on that topic, the role of awareness...once you got the news articles, there's raising money for the foundation for Idan, you started hearing from all these patients and family members who had this condition, and that's where you start getting the numbers you need for not only raising money but also for clinical trials and getting more interest. 


This is something we really want to do at scale for many patient foundations as well. NORD's 40th anniversary, and the anniversary of the rare disease Orphan Drug Act, is next year. I'm just curious to know about your experience working with other foundations -- maybe there's Hyper IgM groups in other countries.  Is it very collaborative? How do you feel the ecosystem has evolved since you started the foundation?


Akiva: When we started it, there wasn't anything with Hyper IgM out there. Later on, there was an Australian mom that started a support group for Australia and we kind of reached out to her right away and wanted to bring her together with us. She's like our patient liaison in Australia and we've joined the support groups together. 


But I have made it a point to be active in the rare disease community, going to conferences, sometimes speaking at conferences. You need to make sure you always have a seat at the table. There's so many times I've gone to a conference and I've met a doctor there that I did not know was focused on researching something that was relevant to what we are doing. That's kind of how it has developed.


Another aspect is that I make it a point to also go to the medical conferences. I'm not a doctor, but I have a background in public health. I've joined a number of societies and I go to their conferences. I am not just an exhibitor, but I'm there to be at the discussions, be at the sessions, talk to doctors, and that's kind of expanded that network and led to a lot of the researchers that we that we end up meeting. Just by being at these conferences, I've connected with doctors that I would have never known and then been able to possibly help their research forward. So, that's been really great.


Shiv: That definitely echoes some of the other folks we've had on. Like, we interviewed Philippe Pakter whose daughter has Pierre Robin Sequence. He speaks at conferences and connected me to people like Nick Sireau who I'm sure you know. It's very interesting how similar a lot of these journeys have been -- though the conditions are so different and circumstances tend to be very different as to when people are diagnosed -- but there are core themes that I think we'd like to get across to our learners and anyone who's interested in the space. 


I know we're coming up on time. What advice would you give more generally to our audience about working with rare disease patients and family members? How can they be most helpful, both to you personally and to Hyper IgM Foundation, and then the rare disease community as a whole, in your opinion?


Akiva: I think for medical students and people that are going through their training, getting involved with any kind of patient organization that is possibly connected to whatever you're planning on specializing in would be an amazing benefit because it would allow you to see a different perspective that's not just in the exam room and not just in the book that you're reading, 


One of Idan's immunologists from Seattle sits on our board and he's become a very close friend. I think that it definitely helps him in his own practice as an immunologist, to be connected to these patients and kind of know their stories from a different side than just the white coat and the patient in an exam room. 


I'm a part of a group called the Primary Immune Deficiency Treatment Consortium which is made up of most hospitals and research centers that treat immune deficiencies, but they have patient advocacy groups as part of it. We're on their monthly calls when they're talking about their research trials and so on. We have our own monthly calls and a lot of their physicians then participate in what we're doing and help collaborate on the research projects we're doing. So, I would say get involved with any kind of patient organization to kind of give you that perspective.


Shiv: Definitely. I love that.  It's very meaningful. Honestly, it's some of the most motivating work for me in the last decade or so at Osmosis, because of the heroic stories of these rare disease patients and family members like yourself and the gratitude for even the small part we play. We want to expand upon that. 


What other topics that I haven't asked you about would you like to cover? Any other final words on your family story on Hyper IgM, or the space as a whole? And then if not, you are more than a parent of a rare disease child. What are the other things that keep you busy? Are you still consulting for health care companies? Are you doing public health work, or is this kind of a full-time job for you right now?


Akiva:  I'm focused now really almost full time on the Hyper IgM Foundation, and just parenting. Parenting in itself should be full time, always. But when the kids are in school, you have time. So I'm focused on helping our community and really trying to grow this organization to a situation where possibly I could step back and it runs without me. That would be ideal. I could still play a part, but it can be large enough that it would run also without my influence, essentially. So that's my focus. 


Shiv: Yeah, that'd be ideal to keep growing not because there's more patients, but hopefully because some organizations are making breakthroughs. One last thing: the hope with any of these rare conditions is that the research that goes under them elucidates some pathways that have even broader applications to anyone with, say, other immune disorders.  Any last words on maybe that potential given how much you know about the research on Hyper IgM?


Akiva: I know from discussions with a researcher out of UCLA that is focused on gene editing for Hyper IgM that the work that she's doing hopefully does lead to a clinical trial with a CRISPR technique that would edit the gene and allow you to have a fully functioning immune system. Because it's a specific gene that is not working properly, you could fix it. She feels that if they're successful there, it would expand to other types of diseases.  I think the funding that she got was because it's a good trial on the science, and then if that works, it could grow and affect a lot of other diseases.


Shiv: Let's hope that comes to pass. It's gonna be very exciting to see what happens over the next decade or so. So, Akiva, thank you so much, not only for taking the time to be with us on the podcast today but more importantly for the work that you've done for the rare disease space and for Osmosis and for connecting us to the space.


Akiva: Thank you.


Shiv: With that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show and remember to do your part to raise the line and strengthen our healthcare system. We're all in this together. Take care.