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Seven Questions for a Rare Disease Warrior

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Francis Collins with David Fajgenbaum
Caption: David Fajgenbaum (right) and I pose for a photo a few years ago in Philadelphia.
Credit: National Disease Research Interchange, Philadelphia

Tomorrow is Rare Disease Day at NIH, marking the 12th year that this annual event has been held on the NIH campus. Similar gatherings have been organized independently around the world this week, all to raise awareness for the nearly 7,000 rare diseases, some affecting just a few dozen people. But, collectively, rare diseases are hardly rare. One in 10 Americans has a rare disease (defined as affecting 200,000 or fewer individuals in the US), and about half are children. Without needed treatments, about 30 percent of these children will die by age 5.

To join everyone in raising awareness, I wanted to feature on my blog a unique perspective about rare diseases, and David Fajgenbaum certainly has one. Fajgenbaum is an immunologist and NIH grantee at the Perelman School of Medicine, University of Pennsylvania, Philadelphia. When Fajgenbaum isn’t running studies or clinical trials, he must remain vigilant of his own health. Fajgenbaum has a rare disease called idiopathic multicentric Castleman disease (iMCD), and this devastating condition, which emerged while he was in medical school, nearly claimed his life several times.

Now 34 years old and in a long remission, Fajgenbaum can discuss rare diseases as a doctor, as a patient, as a researcher, and as an advocate. His personal journey, published in his recent book Chasing My Cure, is a gripping read. Fajgenbaum was kind enough to answer a few of my questions on rare diseases and share some of his lessons learned.

The last time that I saw you, David, you looked great. How long have you been in remission?

I have been in remission for 73.83 months. I say 73.83, because I know that I can’t round up—I may relapse tomorrow. But I also refuse to round down because so many colleagues and I have worked so hard for every day of remission for me and other patients with my disease.

For me, every day is particularly special, because I never thought that I would be alive this long. As you know, I became deathly ill during medical school in 2010 and even had my last rites read to me when my doctors didn’t think I would survive. I was eventually diagnosed with idiopathic multicentric Castleman disease (iMCD), which is like a deadly cross between cancer and autoimmunity. Chemotherapy saved my life, but I would go on to have four near-death relapses.

After one of those relapses, I got out of the hospital and dedicated my life to conducting iMCD research and co-founded the Castleman Disease Collaborative Network (CDCN). Later, I identified a particular cellular pathway called mTOR that was highly active in my samples. I began testing on myself an mTOR inhibitor [sirolimus]—developed 30 years before and approved for kidney transplantation but never considered for iMCD. It’s this drug that has kept me in remission for the last 73.83 months and helped other people. During this time, I’ve been able to marry my wife, have a daughter, help launch a new center at Penn specializing in rare diseases, and write a book to share my personal journey with others.

As a physician-scientist and as a person with a rare disease, what have you learned about the biomedical research process?

I’ve learned so much, but I’d like to highlight three lessons in particular. First, we must leverage all perspectives to prioritize research and give us the best chance of translating research into meaningful breakthroughs. The traditional approach to rare disease research involves a subset of researchers within a rare disease field submitting their best ideas for funding and a panel selecting the best applicant.

Through the CDCN, we’ve spearheaded a new approach called the Collaborative Network Approach, where we crowdsource research questions from the entire community of patients, physicians, and researchers (not just a subset of researchers) and then recruit the best researchers in the world (not just from within the Castleman disease field) to perform the prioritized studies. We’re now working to improve and spread this approach to other diseases.

Second, collaboration between all players is critical. Patient advocacy groups are uniquely positioned to serve as the glue between all stakeholders. Researchers and physicians need to share ideas, data, and samples with one another. Patients need to be actively involved in research question prioritization and study design. Biopharma and the Food and Drug Administration (FDA) need to be engaged early in the process of research discoveries and drug development.

Third, we must leverage all 1,500-plus, existing FDA-approved drugs to help as many patients without any options as quickly as possible. As you know, less than 5 percent of the nearly 7,000 rare diseases have an FDA-approved therapy, but many diseases share similar cellular and genetic defects that could make them susceptible to the same drugs. I’m literally alive today thanks to a drug developed for another disease. How many of the drugs approved for one disease may be effective for many of the 7,000 diseases without any? I don’t know the answer, but I hope we can begin to address this important question and incentivize repurposing.

In your experience, how can people with rare diseases help to advance progress for their conditions?

There is so much work to be done for so many rare diseases. Sometimes it can feel so overwhelming and like “what can I really do?”

But I’ve learned that there are so many ways that we can each contribute and so many incredible examples of advocates who have made a difference for themselves and those that they love. Cystic fibrosis and chordoma are just two of many examples where patient-advocates have been critical partners in transforming their diseases.

People with rare diseases can raise funds for research. Every dollar truly counts. We can work with existing organizations for our disease to ensure that those funds are distributed as efficiently and effectively as possible. If there are major gaps within our rare disease fields that aren’t being addressed by existing organizations, we can start new rare disease organizations (but we should try to avoid this whenever possible). We can contribute samples and data towards research, participate in clinical trials, and share with other patients about our experiences. We can advocate for new drug development and repurposing already-FDA approved drugs for our diseases.

What would you tell other researchers who are studying rare diseases?

I would tell other rare disease researchers that you are doing such important work. You give us hope that a treatment can be identified that will change our lives. It’s an incredible responsibility and incredibly stressful. There are unfortunately far too many scientific questions and diseases with major unmet need for any of us to compete over the use of samples and data. We have to share these within our fields. And we must also work together across rare diseases. We can’t continue to reinvent the wheel; we must share learnings with one another

I enjoyed doing the CastleMan Warrior Flex with you. Tell us more about what it represents?

Doing the CastleMan Warrior Flex with you is one of my favorite pictures. In fact, it’s hanging up in my office.

Castleman disease was named after Dr. Benjamin Castleman, who first described our disease in 1954. We have repurposed the “Castleman” name to be a “CastleMan Warrior” (below is our cartoon mascot). We do the “CastleMan Warrior” Flex to raise awareness for Castleman disease and rare diseases generally—we’re all warriors in the rare disease space.

CastleMan Warrior Flex
Credit: David Fejgenbaum/National Disease Research Interchange, Philadelphia

What are your future plans as a rare disease advocate and as a researcher?

We’ve made a lot of progress for Castleman disease: we’ve advanced our findings about mTOR towards a clinical trial, gained approval for the treatment siltuximab for iMCD, developed diagnostic criteria and treatment guidelines, and invested about $1.5 million into Castleman disease research, which has led to over $7 million in additional funding from other sources.

But we still have important work ahead of us. The treatments sirolimus and siltuximab work for only a portion of all iMCD patients. We need to identify more effective treatments for all forms of Castleman disease.

I will continue to study Castleman disease and other diseases at the intersection of autoimmunity and oncology to gain insights into how the immune system works in myriad diseases. In parallel, I will continue to advocate for the adoption of the “Collaborative Network Approach” to crowdsource all stakeholder perspectives as well as for new models for drug repurposing.

Any other issues that you’d like to address?

I feel a responsibility to share with the world the lessons that I’ve learned about life from nearly dying five times. This is a major reason that I wrote my book.

One lesson that I think about a lot is related to my growing up playing football. Some of my games were extended into an overtime period to decide the outcome. In overtime, every second counts and you’re totally focused on what’s important. I’ve lived with that exact same feeling ever since I had my last rites read to me.

I’ve also learned that humor can be incredibly powerful. You may think that a good laugh may be the last thing that you’d want to do when you’re dying in the ICU. But laughing with the people that I love actually helped me feel like I could transcend my illness, and it helped to connect us.

My greatest regrets on my deathbed were not things that I had done or said. I regretted what I didn’t do or didn’t say and that I would no longer be able to do. I now follow the motto: “Think It, Do It.” In other words, we should reflect on what we’re hoping for and then turn our hopes into action.

Finally, I’ve learned that it really takes a strong team to make a difference in the world, especially against diseases. If it was just me on my own, we would have made less than 1 percent of the progress that’s been achieved. I hope that all rare disease warriors will join together into strong teams, armies even, and make a difference in the world.

Links:

Multicentric Castleman Disease (Genetic and Rare Diseases Information Center/NIH)

Castleman Disease Collaborative Network (Paso Robles, CA)

His Doctors Were Stumped. Then He Took Over (New York Times, February 4, 2017)

Video: Chasing My Cure: Dr. David Fajgenbaum’s Lessons From His Rare Disease And On Finding Cures For Others (Exponential Medicine, November 4, 2019)

Rare Disease Day at NIH 2020 (National Center for Advancing Translational Sciences/NIH)

10 Comments

  • Mary says:

    How can some with cancer not successful with treatments join a study?

  • Barry J Barclay says:

    Awesome and inspiring story.

  • Diana B. says:

    While I’m so grateful that David is in remission and, possibly a treatment, there needs to be more! There is a group of us who have banded together on FB that have DISH. We have NO doctors who are aware of it. Even though it’s been around for many years. None of the “specialists” we are sent to have correct information and send us home with ” it’s not that painful, take Ibuprofen and keep moving”. Live in my body for 24 hours! It’s world wide and no ones doctors have a clue! There are over 2,000 in my group and we add more daily. Sure, we may not die from it, but our lives can be a living hell.

  • Julie Lima says:

    I had the good fortune to stumble upon Dr. Fajgenbaum’s talk at this past year’s joint Health Datapalooza/National Health Policy conference. Inspired not only by his personal story and his strength, but by his description of the Collaborative Network Approach, I ordered two copies of his memoir before the day was done. I look forward to following Dr. Fajgenbaum’s progress on all fronts and want to thank him for his dedication to others’ wellbeing, not only through the CDCN but his AMF work across college campuses as well.

  • Char S. says:

    Terrific interview. I’m very moved by Dr. Fajgenbaum’s story and his commitment to research. Thanks for all that the NIH does to continually make new discoveries in rare diseases. And finally, Dr. Faigenbaum’s “lessons he’s learned from his experience” closely resemble those of our son, a cancer survivor when he was only 14. He had a relatively rare pediatric cancer and the cure was pioneered at NIH. He thrived on humor — and still does as a young adult. Good work.

  • Eileen Falchetta says:

    Great interview about Dr. Fajgenbaum. The photo used is actually from an event that we held to honor Dr.Collins- this year, that same event will honor Dr. Fajgenbaum- it is our “Service to Science Dinner.’

  • kimpaul777 says:

    Thank you Dr. Collins, you have long been a superhero in my reality…geneticist and musician too! I can only speak from my personal experience, but the long road to diagnosis was nearly fatal seven times for me and spanned a decade. It was fraught with a digital trail that followed me from physician to physician, apprising practitioners that I was a hypochondriac. I was finally found to be on the acute end of the Gitelman’s Syndrome spectrum. I am so grateful for every breath, and spend as much of each day in prayer as possible, towards diagnosis of rare diseases, for those who still remain without. I am further grateful to have been internally driven to NIH and afforded access through an NHGRI internship that extended to bioethics/Bldg. 10, then further out to being the 1st Blackfeet woman to earn a STEM PhD (Biochem, Biomed Sci, Community & Public Health) and now to be nominated for NIH TAC. Thank you Gitleman’s Syndrome, for pushing me towards a lifetime of service to others seemingly stuck in the challenges of un or misdiagnosis, or the diagnosis of a rare disease! Thank you Dr. Collins and NIH for making concerted effort and headway in the science towards improved quality of life and cures!

  • Franziska says:

    that helped me a lot.
    thank you

  • Pam says:

    My granddaughter has a rare disease RAS-associated autoimmune leukoproliferative disorder (RALD) She has a mutated K-Ras gene. Took 6 1/2 yrs for a diagnosis supplied by NIH. We love NIH and all they do to help people with these diseases.
    She was on sirolimus to help her grow and begin puberty. It also helped with other aspects of the disease. During the time she was on it she also was Dx with epilepsy and was continually having severe sores in her mouth, along with abd pain.. Since she began having periods about 4 mths ago her oncologist with her mother decided to stop the sirolimus recently. Unfortunately her blood work was again abnormal again. Our hope is her quality of life will be better without the extreme pain and inability to eat she has with the sores. Her blood work is done quite frequently and NIH also receives a copy. Being sick since she was 1 yr old has made her a very strong empathetic person with a desire to become a researcher and work with children with rare diseases at NIH. She has remained on that pathway since Dx a week after turning 8 and she will be 16 in June. She is not a complainer and yes humor is a daily activity. I hope some day she will be such a dedicated researcher as you have become.

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