Rare As One

Leveraging the Power of Patients to Accelerate Rare Disease Research

Chan Zuckerberg Initiative Science
10 min readJun 11, 2019

Two years ago, I heard an inspiring talk by a remarkable patient and medical professor — David Fajgenbaum. David was a third-year medical student in 2010 when he was struck with a rare disease called “idiopathic Multicentric Castleman disease” that sent his immune system into hyper-drive, causing his organs to shut down. David survived, but suffered a series of relapses over the next few years that each time brought him to the brink of death.

During periods between relapses, David learned all he could about his disease. He found that, despite the fact that Castleman disease had been identified back in the 1950s, the disease was still poorly understood, and the few researchers who were actively working on the disease were doing so in isolation. David decided he would dedicate the rest of this life to driving forward progress against this disease and that he needed to start by building a community.

David knew that to make progress against his disease, he needed to encourage researchers to work together. So he emailed every researcher and clinician that had ever co-authored an article that mentioned Castleman disease and asked them to join a discussion board. It worked — today, the Castleman Disease Collaborative Network is made up of more than 1,400 patients, researchers, and clinicians from around the world, working to identify and set research priorities, fund high-impact research projects, and collect and share tissue samples and data. Collaborations resulting from this network have transformed the community’s understanding of this disease. They also may have saved David’s life — and the lives of many more patients.

Early discussions across this network led to the emergence of a new model for understanding the disease that coincided with David’s fourth relapse. Taking cues from the emerging science and studies he ran on his own samples, David persuaded his doctor to prescribe him an immunosuppressant that had never been used in treating idiopathic multicentric Castleman disease. He recovered and has been in remission ever since.

Dr. David Fajgenbaum, patient and co-founder of the Castleman Disease Collaborative Network to accelerate research and treatment for Castleman disease. Photos by Joanna Rudnick/CZI.

David’s story was one of a number of patient stories that were top of mind for me when I joined the Chan Zuckerberg Initiative (CZI). At CZI, our aim is to support the science and technology that will make it possible to cure, prevent, or manage all disease by the end of the century. David and other patient leaders have taught us that in order to succeed in this mission, we must leverage and bolster the power of patients in our efforts.

This is not a nice-to-have — it’s a must have. So, over the past 18 months, we’ve been meeting with dozens of patient organizations, advocates, researchers, clinicians, and others to understand the needs and capacities of patient communities. We’ve learned that patients and their loved ones are taking on ever-expanding roles and responsibilities in accelerating research — developing deep knowledge about their disease and building research networks, registries, and biorepositories to drive research forward. These efforts can be enormously impactful, especially for rare diseases that are typically underserved by the traditional academic research model. Today, with the launch of the Rare As One Project, we are committing to partnering with the rare disease community to lift up patient-led research efforts and work toward the development of a shared infrastructure that enables all rare diseases to benefit from this approach.

The Challenge: Rare As Few

Collectively, rare diseases are anything but rare: as many as 7,000 rare diseases affect approximately 400 million people worldwide. Yet, for an individual patient and their loved ones, the experience of living with a rare disease can be isolating. The road to diagnosis is often long and daunting, as patients go from doctor to doctor, searching for answers. And the ultimate diagnosis — while critically important — seldom points to a clear plan of action.

30 percent of children with a rare disease will not live to see their fifth birthday. Photo by Joanna Rudnick/CZI.

Fewer than five percent of rare diseases have an FDA-approved treatment.

Why are there so few treatments for rare diseases? A big reason is that the underlying biology of the vast majority of these diseases is poorly understood — and it’s hard to treat a disease if you don’t understand its biology.

The barriers to advancing our understanding of the biology of rare diseases, however, are not fundamentally scientific. The primary challenge comes down to numbers. For any given rare disease, the small number of patients means that very few of them are seen at any given academic research center. A researcher who wants to study a rare disease needs to collect enough data and specimens to sufficiently power that study, either by identifying and engaging patients directly from around the world or entering into complex data- and specimen-sharing agreements with multiple institutions. These efforts can be exceedingly time- and resource-intensive and give rise to legal, practical, and operational challenges that can prove insurmountable.

Even where the basic biology of a rare disease is generally understood, incentives may not be sufficiently aligned for pharmaceutical companies to invest in developing a drug and bringing it to market. A number of public programs, regulations, and policies have helped to create incentives for R&D investment in rare disease therapeutics, but at the end of the day, small patient populations cannot provide the large markets that are afforded by common diseases.

The Hope: Rare As Community

More and more, rare disease patients and their loved ones are seeking to address these challenges head on. Faced with a dearth of information about their disease, they are taking it upon themselves to unite their communities and drive the research forward.

When Tracy Dixon-Salazar’s daughter Savannah was five, she was diagnosed with Lennox Gastaut Syndrome — a severe form of epilepsy. Tracy got her PhD and found a treatment to help improve Savannah’s life. Photo by Joanna Rudnick/CZI.

At CZI, we have set out to better understand these efforts. Through discussions with dozens of patient advocates, we’ve learned that patients and parents of children with rare diseases are turning devastating news into opportunity and action, passionately re-purposing their backgrounds and skills — and learning altogether new ones — to advance research. They are leveraging social media platforms and other technology to identify and engage other patients from around the world. They are sharing their deep knowledge and insights about their disease with researchers and clinicians, and developing a sophisticated understanding of the state of the science. They are telling their stories, bringing awareness to their disease, and raising critical funds for research. They are answering surveys, donating their data and specimens to research, organizing the research community and research priorities, and building sophisticated patient registries and biorepositories.

These discussions have been enormously inspiring, and have crystallized for us some of the reasons why rare disease patients can be such a powerful force in driving research:

1. They bring critical insights about their disease to the table.

Some — like Tracy Dixon-Salazar and husband and wife team, Sonia Vallabh and Eric Minikel — went back to school to become researchers and are contributing directly to the field. Others have developed key insights from living their disease day-to-day and interacting with other members of their community, and are sharing those insights with researchers to inform scientific directions. All are experts in their own right.

2. No one is more motivated than patients to drive progress against their disease

And there are many ways they can advance the cause: Maria Kefalas founded the Calliope Joy Foundation and sold 45,000 cupcakes to start a clinical research center for her daughter’s disease; Megan O’Boyle built a patient registry for Phelan-McDermid syndrome that connects more than 1,800 families from around the world; Josh Sommer stood up the Chordoma Foundation that created a patient-led biobank, disease models, and other research-enabling infrastructure than has catalyzed discovery of more than 20 drug targets and a pipeline of seven new clinical trials in just 10 years.

Maria Kefalas (far right) founded the Calliope Joy Foundation and sold 45,000 cupcakes to start a clinical research center for her daughter’s Cal’s disease, called leukodystrophy. Photo by Joanna Rudnick/CZI.

3. Rare disease advocates are committed to a cause beyond themselves.

They understand that the work they are doing may not help them, or their child, directly. Some, like Pat Furlong, founder of Parent Project Muscular Dystrophy, continue to lead advocacy groups long after their children have succumbed to a disease. This commitment to making things better for future patients is inspiring and critical for sustaining progress.

Our conversations to date have also taught us that, while each rare disease is different from the next, and has its own set of challenges, the approach that patients are taking to accelerate research typically follows a progression of discrete stages: obtaining a diagnosis; building a patient community; organizing a community of researchers; building a patient registry; collecting biospecimens; funding research; and engaging industry. The small but growing number of rare disease groups that have successfully navigated these stages have fueled significant discoveries in their disease areas that have led to the development of new disease models, diagnostic criteria, drug targets, clinical trials and even new therapies in a remarkably short period of time.

Nasha Fitter with her daughter Amara, who was diagnosed with FOXG1 syndrome. Along with two other mothers, Nasha founded the FOXG1 Research Foundation, dedicated to finding a cure for all children with FOXG1 syndrome, and perhaps even for brain disorders at large. Photo by Joanna Rudnick/CZI.

At the same time, patients seeking to follow this approach face significant barriers at each of these stages. Despite advances in genetic sequencing and other technology, time-to-diagnosis typically takes several years. Diagnosis allows patients to find one another, but too often, communities are fractured through formation of multiple organizations, and competition for resources dilutes progress. Building a patient registry and/or biobank is enormously time-consuming, and requires assessing an array of third party platforms and navigating complex financial, legal, and ethical issues. Understanding what research to fund tomorrow requires a solid understanding of what is known today, but that information is rarely systematically assembled and updated. Without a clear roadmap, patient communities are “reinventing the wheel,” rather than learning from one another. As a result, the potential for patient-led research remains largely untapped.

The Promise: Rare As One

CZI is committed to helping address these barriers. We believe that doing so will require that research move away from a disease-by-disease approach. Through the Rare As One Project, we will work in partnership with the rare disease community to create a “virtual incubator” in the form of shared infrastructure — funding programs, tools, training and other capacity-building resources — to lower the barriers to patient-led research and enable patient communities to learn from one another.

To begin, we’re launching a funding opportunity for patient-led rare disease 501(c)(3) organizations to apply to join the Rare As One Network. This initial, two-year grant program will fund up to 10 organizations to build and sustain collaborative research networks of patients, researchers, and clinicians working together to develop shared research priorities. To learn more and apply, please visit our website.

The ultimate goal of the Rare As One Network is not to fund 10 rare disease groups; it is to work with this initial cohort to test and iterate on this approach to create and sustain a patient-led research network. The individual networks that are created under this initial grant program will be part of a larger learning network from the start: we’ll ask that they share feedback with other rare disease groups, learn from one another, and identify how to best address the most pressing needs across a spectrum of rare diseases. Over time, we hope to expand the incubator to provide assistance to a broad array of rare disease groups at different stages of development.

At CZI, we believe that solutions to problems lie with the communities we are aiming to serve, so we are building out our program in partnership with rare disease organizations. We’re working with the Castleman Disease Collaborative Network to inventory the tools and capacity-building resources that they and other patients groups are currently using to build and sustain patient-led research networks and identify gaps. We’re working with Global Genes, an organization representing more than 500 rare disease organizations, to develop interactive workbooks to guide organizations on building and sustaining patient-led research networks and registries. We’ve also funded the Rare Genomes Project at the Broad Institute to help scale a direct-to-patient effort to accelerate diagnosis for patients with rare, undiagnosed genetic diseases. And we’ve funded Pattern.org to broaden its capacity to provide rare cancer patients with the opportunity to direct their tumor samples to research.

Mileva Repasky and her daughter Katie Repasky, who was diagnosed with Castleman disease. Photo by Joanna Rudnick/CZI.

CZI is just beginning its work in this area. We are enormously grateful to the dozens of patient advocates, organizational leaders, researchers, policy experts, and others who have guided our efforts to date and have served as inspiration for this program. We look forward to learning from many others and working in partnership with this extraordinary community to leverage the power of patients and maximize and scale their impact in our collective fight against disease.

Tania Simoncelli, CZI Science Policy Director and Rare As One Project lead

For the past 20 years, Tania Simoncelli has designed advocacy strategies and policy solutions to address complex issues at the intersection of science, technology, law, and ethics. In 2017, Simoncelli joined the Chan Zuckerberg Initiative as Director of Science Policy, where her work focuses on enhancing public support for science and building an initiative to promote patient-driven disease research at scale. Previous roles include positions at the Broad Institute of MIT and Harvard, the White House Office of Science and Technology Policy, the U.S. Food and Drug Administration, and the American Civil Liberties Union. In 2013, Simoncelli was named by the journal Nature as “one of 10 people who mattered” for her work in spearheading the ACLU’s successful Supreme Court case challenging the patenting of human genes. She holds a B.A. in Biology and Society from Cornell University and an M.S. in Energy and Resources from UC Berkeley.



Chan Zuckerberg Initiative Science

Supporting the science and technology that will make it possible to cure, prevent, or manage all diseases by the end of the century.