How Patients are Driving Rare Disease Research for their Loved Ones


For Ricky Safer, being diagnosed with a rare disease in 2003 was an isolating experience. Doctors knew little about the cause of her illness, primary sclerosing cholangitis (PSC), which afflicts the liver in 1 in 10,000 people in the United States. There was — and still is — no cure.

So, she sought out other people with her condition and, with their help, founded PSC Partners Seeking a Cure. Now, with support from CZI, this patient-led group and dozens like it have been building powerful communities: wide-reaching networks that include not only patients but also scientists, doctors, and drug developers. These organizations are helping to break down research silos, create disease registries and clinical care guidelines, and spark new research and the development of treatments in their disease areas.

The PSC Annual Conference at Mayo Clinic. Photo courtesy of PSC Partners Seeking a Cure.

In short, they have been working to make sure that no one has to go through what Ricky Safer did. “If you are a person with a rare disease,” she said, “you do not have to be alone.”

CZI launched its Rare As One Network three years ago with the aim of enabling and scaling patient-driven research and discovery in rare disease. We initially selected 30 organizations to support, work with, and learn from. Through a combination of funding, capacity building, training, and fostering collaboration, we’ve helped groups scale up, come together, and find new pathways forward.

Now expanded to 50 organizations, like PSC Partners Seeking a Cure, the Rare As One Network organizations are having a direct impact in accelerating research.

Consider Congenital Hyperinsulinism International (CHI), founded in 2005 to combat an illness marked by severe hypoglycemia that can cause brain damage in babies if not diagnosed quickly. In September 2021, CHI held a virtual convening attended by 216 people from 34 countries. This event brought together researchers, advocates, and clinicians from academic and non-academic settings to address the disease, importantly putting patient voices front and center.

Building on the work of this conference, researchers published three papers the following year using patient-reported outcomes, a first in the scientific literature for this disease. Also written were the first-ever globally accepted care guidelines for the disease, which ensure that patient experiences and opinions about treatment are factored into care decisions. CHI built a network of researchers that have been exploring the basic biology of the condition: some of the researchers in the network have linked a previously unrecognized gene to the disease, as detailed in Nature Genetics. Other network members have probed deeper into the molecular mechanisms behind the high insulin and low glucose levels thought to underlie the damage done by the disease.

Baby Shaquille is one of the reasons Congenital Hyperinsulinism International is working on a worldwide campaign to recognize glucose as an essential vital sign to monitor in newborns. Photo courtesy of CHI.

“This knowledge will help up to 40 percent of all babies that have irregular patterns of insulin regulation at and soon after birth,” said Julie Raskin, co-founder of CHI. The work is personal for her because she’s the mother of a child with the disease.

CZI’s initial support not only helped our first cycle of Rare As One grantees accelerate research; it has been a stepping stone to enabling them to scale their impact.

For Cure HHT, that meant receiving several million dollars from the Health Resources and Services Administration (HRSA). For more than three decades, this nonprofit has been working to combat hereditary hemorrhagic telangiectasia (HHT), a genetic blood vessel disorder that causes sudden brain and lung hemorrhage and bleeding in other organs. The HRSA funding enables Cure HHT to launch a professional registry that will systematically collect data from people with the disease at 32 care sites across the country, a key instrument for a natural history study and furthering clinical research. This comes on the heels of creating a new therapeutic arm of Cure HHT, developed with guidance from a CZI-organized mentorship program, that facilitates closer collaboration between the medical and scientific communities.

“We have been able to accomplish so much more as a connected community than we ever could on our own,” said Marianne Clancy, executive director of Cure HHT. A patient herself, Clancy was motivated by the sudden loss of her sister and mother to HHT. She joined Cure HHT in its early stages and has counseled thousands of patients and families who have lost loved ones and children from a lack of a diagnosis or improper medical treatment.

Marianne Clancy. Photo courtesy of Chan Zuckerberg Initiative.

The DADA2 Foundation will also be launching a patient registry. Deficiency of Adenosine Deaminase 2 (DADA2) is a rare genetic disease discovered only eight years ago that can cause recurrent strokes, severe inflammation, immune deficiency, and potential organ damage. The DADA2 Foundation will soon publish a paper outlining best practices for the diagnosis, treatment, and management of the condition. After building relationships with researchers and biotech, the group hopes to identify new treatments for development.

DADA2 usually starts in childhood and causes recurrent strokes and severe damage to many of the body’s tissues and organs. Launched by parents of children with this rare disease, the DADA2 Foundation brings together researchers and clinicians from around the world to accelerate research, identify treatments and find a cure so that patients and families can live more full lives. Photo courtesy of DADA2.

“We believe that collaborative science is the way to solve science and medicine’s biggest challenges,” said Chip Chambers, DADA2 founder and president, who is also a doctor and parent of two children with DADA2.

While helping to strengthen these communities through the Rare As One Network, we have noticed a powerful network effect. Rare disease organizations are learning from one another, sharing resources, tools, and approaches, and co-developing strategies together. For example, many have adopted an online forum that allows their community to crowdsource and prioritize research ideas — a tool developed by the Castleman Disease Collaborative Network, a patient-led organization dedicated to a group of rare immune system diseases that involve enlarged lymph nodes and a broad range of inflammatory symptoms. KIF1A.ORG, which tackles diseases linked to the KIF1A gene, expanded on this initial design to build a formal Resource Hub that includes a resource library, discussion forum and other features to engage and support researchers. Additionally, many of the organizations have worked to bring their research communities together on a regular basis through a research roundtable series.

The Rare As One Network at the June 2022 Annual Meeting.

What works in one community may not always work in another. But the Rare As One Network organizations are elevating an approach to rare disease research where patients are centered. They are leading the charge, bringing their unique insights and understanding of their disease to the table and demonstrating that this approach can deliver rapid progress toward developing treatments and cures to fight against the thousands of rare diseases affecting millions of people worldwide.

CZI offices illuminated for Rare Disease Day 2023.

Learn more about the work of our grantees fighting to find treatments, therapies, and cures for all rare diseases.



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.