Connor was born in 2007, the third sweet child of the Raymond family. He missed some important milestones: Sitting up, walking, and talking were particular challenges.
At 2 years old, Connor had his first seizure.
“Katia, my wife, and I didn’t know what was going on with him, neither did his doctors,” recalls Connor’s father, Michael Raymond.
Connor started taking seizure medication. Three years later, he fell coming out of Sunday school.
“He reached out his arm and it looked like someone had taken a baseball bat to it,” Raymond says. “He had broken both bones in his forearm.”
Hailing from Northern Virginia, Connor’s parents took him to Children’s National in Washington, D.C. It wasn’t until he had a whole exome sequencing test that they were able to identify his condition: Snyder-Robinson Syndrome (SRS).
At the time, 5-year-old Connor was only one of a handful in the country diagnosed with SRS, a rare genetic condition characterized by intellectual disability, muscle and bone abnormalities, and developmental delays. The Raymonds had never heard of it, and neither had any of their friends. Although alarming, Connor’s father says he was partially relieved.
“At least knowing what it is, we could try to start working on it,” Raymond explains.
The time it took for Connor’s diagnosis is unfortunate, albeit typical, of patients with rare, also called orphan, diseases. Primary care doctors likely haven’t been exposed to many rare diseases—there are an identified 7,000 in the world. And although rare diseases as a whole affect 30 million people in the U.S., many of whom are children, each disease targets fewer than 200,000 individuals, making them usually neglected by established research and drug development enterprises, and unnoticed by the general public.
And, to top it off, researchers working on rare diseases have historically worked in isolation. The disorders are so rare, and research teams so small, that they aren’t often aware of what colleagues are working on beyond their own institutions.
It’s all of these reasons and more that Penn’s Perelman School of Medicine established the Orphan Disease Center (ODC) in 2011, the only one of its kind, to promote the development of therapies for a variety of rare diseases. With six years under its belt, the ODC has raised millions of dollars for rare disease research and made significant headway in connecting experts worldwide in rare disease fields.
‘A center without walls’
The ODC was founded with a $10 million gift from philanthropist and Wharton graduate George Weiss, who had a young family member who was diagnosed with a rare disease. From its inception, Weiss had a unique model in mind for the ODC.
“Our mandate from George was to be outstanding in all aspects of our basic, translational, and clinical research,” says James Wilson, the ODC’s director and a professor of medicine. “To accomplish this for a rare disease, we have to reach outside the walls of Penn to assemble a critical mass of scientists, physicians, and patients. We view ourselves as outwardly facing—a center without walls.”
Monique Molloy, the ODC’s executive director, says 80 percent of the funding the ODC raises goes outside of Penn, and its partner the Children’s Hospital of Philadelphia, “and we’re proud of that.
“Not a lot of places can say that,” she adds. “We’re just looking to fund the best science. It’s a big part of who we are.”
But that doesn’t mean Penn lacks leaders in the rare disease space. Penn Medicine researchers, including Jean Bennett, Mark Haskins, Frederick Kaplan, Reed Pyeritz, Daniel Rader, and Vera Krymskaya, among others, have been developing programs of excellence on inherited forms of blindness, storage diseases, and liver metabolic disorders, to name a few.
Wilson himself is credited for being at the nexus of gene therapy since its birth, a logical way to treat rare genetic diseases. And then there’s David Fajgenbaum, a Penn Medicine assistant professor and the ODC’s associate director of patient impact, who is battling a rare disease himself.
When Fajgenbaum was 25, and a third-year medical student at Penn, he landed in the hospital—organs failing and on the verge of death—for what he’d find out months later was Castleman disease. Three life-threatening relapses later, he decided to dedicate his life’s work to fighting the debilitating disease, of which he has the deadliest subtype.
Throughout the years, while he finished his medical degree and went on to study at the Wharton School for an MBA, Fajgenbaum monitored his rare disease closely, collecting weekly blood samples. When he relapsed again, he was able to pinpoint the suspected reason why.
“It’s an immune system disorder,” Fajgenbaum explains. “The immune system becomes too strong and too activated. It attacks your liver, bone marrow, and kidneys in a relentless fashion.”
Fajgenbaum needed a treatment that would suppress his immune system. He and his doctors landed on Sirolimus, commonly used to prevent organ transplant rejection but never used before for Castleman disease.
The drug has shown promise for Fajgenbaum, as he recently crossed a major milestone. June 5 marked 82 months since he first became sick from Castleman disease. In his first 41 months, he had five critical flare-ups requiring months of hospitalization. Ever since starting Sirolimus, he’s been in remission.
“I’ve been healthy for 41 months, an equal amount of time that I was sick,” he says.
Working with the ODC, Fajgenbaum, who also runs the Castleman Disease Collaborative Network, says he can easily share the progress he’s made, and learn from the work of others in the rare disease space.
“The ODC is so uniquely positioned to bring different groups together from across the spectrum,” he says. “We need to fight these rare diseases individually and collectively, and help people understand how important they are. No disease is too rare, especially when it affects someone you love.”
Bike for a cure
The ODC’s biggest fundraising event is its annual Million Dollar Bike Ride (MDBR). Every spring since 2014, more than 25 cycling teams representing different rare diseases challenge themselves to ride 13, 34, or 72 miles across the Philadelphia area. In its first three years, the event, always held in May, raised $3.5 million.
This year, and in years’ past, even the rain couldn’t keep the teams away.
“The weather never matters,” says Molloy. “They’re always there to support their community. It’s shining a light on something that doesn’t otherwise get attention. It’s really exciting.”
Once a MDBR team raises a minimum of $20,000, the ODC, funded completely by philanthropic and corporate donations, promises to match it dollar-for-dollar up to $50,000. The ODC then distributes the funds to those of the highest scientific merit, and manages the progress.
In 2016, Raymond’s “Team Snyder-Robinson Syndrome” raised $50,000, and the ODC matched it, making its total funds $100,000. Two grants were later awarded to Charles Schwartz of the Greenwood Genetic Center in South Carolina and Fernando Fierro of the University of California, Davis. This year, so far, Raymond’s SRS team has raised $40,000. He’s hoping to raise another $10,000 by the end of the month, when the campaign officially closes, and see another $50,000 match from the ODC.
Fajgenbaum’s “Team Castleman Disease” has raised close to $150,000 throughout the past three years through the MDBR and ODC, “each year tripling the funding that was previously provided annually for Castleman disease research,” he says.
Also, a day before the MDBR, the ODC always hosts a symposium for rare disease patient advocates.
“It’s not so much about how you cope with your rare disease,” says Fajgenbaum, who organizes the symposium. “But it’s very much about how to take on your rare disease. How to make progress scientifically and from an awareness perspective. And how we can all work together.”
Raymond described the symposium as simply “incredible.”
“The speakers are so inspiring, and the information you get and learn about is just invaluable,” he explains. “It helped us get plugged in with researchers at Jackson Labs and with a pharmaceutical company that’s developing a cancer drug that may also help SRS patients. So the symposium creates a really wonderful snowball effect. We’ve made a giant leap in SRS research just following the advice given at the conference.”
Symposium participants get a feeling, Raymond explains, that no matter how rare your disease is, this community is here to help.
“There’s nothing else like this in the world,” he says. “It’s so unique and special. If we’re going to find a treatment, or a cure, this is how it’s going to happen.”
One of the ODC’s most recent plans, announced this spring, is to collaborate with Pulse Infoframe, a medical informatics company, to develop rare disease patient registries aimed at enabling international collaboration.
The registries, which will begin tackling CDKL5 Deficiency and Crigler-Najjar Syndrome, will serve as a uniting platform for global rare disease patients, foundations, pharmaceutical and biotechnology companies, and academic communities, undoubtedly allowing better understanding of these diseases, and accelerating clinical studies to develop new therapies.
“These are databases that patients can contribute information about their own cases, such as medical data, so that we can find patterns across hundreds of patients,” says Fajgenbaum, who already spent three years creating a registry for Castleman patients.
“It’s such an important initiative serving an unmet need,” says Molloy. “This is what’s going to bring people with rare diseases together, and the sky’s the limit with 7,000 diseases.”