The reality is that with nearly 11,000 identified rare diseases, with many that have only dozens of diagnosed patients, the economics of drug discovery and development simply don’t work within existing business models.
But don’t tell that to the parents and family members of kids born with a rare disease. Frustrated by long diagnostic journeys, doctors uninformed on the specifics of their patient’s rare disease, and the lack of treatment options or any meaningful therapeutic development, have activated a small corps of hard-driving, activist parents not willing to take no for an answer. Driven to improve the lives of their rare disease kids, these parents are positively affecting the lives of the broader rare disease community, while pushing the envelope to find treatments and, perhaps, eventually cures.
As such, parents are a significant driving force behind advances in rare disease management and treatment, and are illuminating opportunities for the industry to stick their toe in the water to further advance the field.
Here, we profile three such parents whose commitments to their cause are impacting the rare disease community.
The community builder
For some parents of children with a rare disease, the symptoms slowly emerge over time, but in other instances it can be apparent very soon after birth that the child has a health issue that needs to be addressed.
Such was the case with Ford Parks, now six years old, the son of Effie Parks and her husband Casey. Ford was a low birthweight baby who immediately exhibited difficulty with sucking and swallowing. But when his parents approached doctors about their son’s difficulties, they were initially told nothing was wrong, it was simply a case of them being new parents and not knowing what they were doing. Or, they were told he was colicky and would eventually catch up with the growth and development milestones he wasn’t hitting.
This merry-go-round lasted about four months until the pediatrician finally agreed Ford had a health issue and admitted him to Seattle Children’s Hospital. During his hospital stay, Ford underwent a series of tests and, after attempts to feed him proved futile, was released a week later with a feeding tube, but no definitive diagnosis.
Testing continued for the next year, and eventually Ford was diagnosed with a rare genetic disease called CTNNB1 syndrome, which is a severe neurodevelopmental disorder caused by disruption of chromosome 3p22.1 of the CTNNB1 gene. First diagnosed 10 years ago, CTNNB1 syndrome has been identified in only about 300 people around the world, though there are likely more undiagnosed cases.
“Once you have a child who’s diagnosed with a rare disease, your whole life kind of implodes,” says Effie. “You’re thinking about all of these things that you thought were going to be that aren’t ever going to be and that creates a lot of turmoil.”
In Effie’s case, she had six friends who also delivered their babies around the same time Ford was born and she admits to feeling very isolated. “While they were packing snacks and going to the park, I was figuring out a feeding tube pump and going to four doctor appointments a day.”
Effie says she has always been a very upbeat and high-energy person, but felt herself slipping into a sadness and a malaise that left her disconnected from friends and the world around her. Faced with the myriad challenges and mental stress of caring for a very sick child, she did what many parents of kids with rare diseases do: searched endlessly online for more information about her child’s disease and for people in her situation that could provide support.
Eventually, she found a short podcast series that resonated. “It was people talking about their day-to-day and it was like someone understood me. I finally felt seen, and I found some hope,” she says. It was this experience, Effie says, and the scarcity of information that “compelled” her to find a way to be a part of the conversation about what it is like, day in and day out, to be the parent of child with a rare disease.
“I knew it was a hole that needed to be filled,” she adds, “because everything was so disjointed, and finding what I needed was almost impossible.”
Effie also realized she could be an advocate, resource, and reassuring voice not just for the CTNNB1 syndrome community of families, but for all the people who have a family member with a rare disease. With this mission in mind, she launched the Once Upon A Gene podcast. It’s first episode published the last week of October 2019, and she has produced a new podcast weekly since then for a total or more than 160 episodes.
Almost immediately, Once Upon A Gene struck a chord within the rare disease community. Episodes routinely top more than 10,000 listens per week and include first-hand accounts from other rare disease moms and dads tackling issues such as the strains placed on personal relationships, how to work with schools, or how to access critical healthcare benefits, among others.
Effie also credits the podcast medium itself as being perfect for this audience. “It’s a practical thing,” she notes. “I know that I was in the car in traffic, or in a doctor’s waiting room for 90% of my days, so reading books and blogs, or attending webinars were not an option. A podcast is so digestible, and people can come back and listen to something again if it resonates.” But it was more than just the practicality of working within the confines of the hectic schedules of rare parents and families. Hearing the voices of others in similar situations provides an almost personal connection to the stories being told.
“Even if they don’t know you, you feel like you end up knowing them,” Effie says. “It created these passive friendships that people can dip into when they need it.”
Now more than three years after its launch, Effie says she still learns something from each episode she produces and the story she helps her guests tell. And with so many episodes available, she sees the archives as a “cafeteria” of sorts, where people can browse the archives and listen to those that are most compelling based on their individual experiences. “I feel like I’m a connector to the rare advocacy community that I’ve built, a community that didn’t exist when I had Ford,” she says.
Through it all, Effie has found that the people driving many of the advances in rare disease are those personally affected by them. “Rare disease families and the patient advocacy groups are the ones who are driving forward research and advocacy and our data is invaluable,” she concludes. “I would encourage any family to poke around in places like Once Upon a Gene, and to think about what you need in your life, whether it is self-care, or advocating at the doctor, or deciding if you want to fund research. Then just listen, and contact the people that speak to you, because they’re going to support you if you want to help.”
Having a child with a rare disease, especially one that is highly debilitating, often results in one of the parents leaving their job to care for the child. Such was the case with Mike Graglia, whose son Tony was diagnosed at four with SynGAP1 syndrome—a genetic disease that results in dysregulation of proteins that help control the activity of synapses in the brain—which results in an array of neurological symptoms.
Like many parents whose child is finally provided with a definitive diagnosis to their health condition, Mike dove into researching all he could about SynGAP1. During this, he quickly became connected to leaders in SynGAP1 research including Richard Huganir, the director of the Department of Neuroscience at Johns Hopkins Medicine, who first discovered the SynGAP1 gene in a mouse study 20 years earlier; noted epileptologist Daniel Lowenstein of the University of California San Francisco who was one of the driving forces behind the creation of the Epilepsy Phenome/Genome Project (EPGP); Heather Mefford a neuroscientist at St. Jude Children’s Hospital whose lab focuses on pediatric neurological disease research; and Annapurna Poduri of Boston Children’s Hospital, a physician-scientist and leader of lab conducting long-term research projects focused on severe early-onset epilepsies.
In addition to connecting with the leading researchers of SynGAP1, Mike was meeting parent-advocates who had started rare disease-focused foundations including Matt and Kristen Wilsey founders of Grace Science Foundation, named after their daughter Grace who suffers from the genetic disorder NGLY1 deficiency, and Maryann Meskis, co-founder and executive director of the Dravet Syndrome Foundation.
Early on, Mike was focused on research that could lead to a cure for kids with SynGAP1 syndrome, but soon learned a sobering truth about the rare disease landscape. Because SynGAP1 syndrome was not a fatal disease, unlike many other rare diseases with high mortality rates, it would be very difficult to interest either drug developers, or regulators, to push right away for a treatment. A conversation with multiple researchers and advisors helped set the course for SRF.
“Essentially they said: ‘Your kid is not that bad, and everyone wants to treat Dravet syndrome. It’s bigger. It’s better understood. Wait for people to cure Dravet in five or 10 years and then maybe they will work on other things like SynGAP1,’” Mikes recalls. “Our back of envelope plan then became to push the science, to make five to 10 years become two to five years.”
From this base, the path forward for Mike and his wife Ashley Evans—a partner in a venture capital firm—became clear: they would create a foundation to raise money and patient awareness while funding new SynGAP1 research.
“I’m a finance guy, and my wife is an investor,” Mike explains. “Our idea was straightforward. We would build a fund to support research, seed it with a million bucks and use that to catalyze raising more money.”
With this basic mission, they launched the SynGAP Research Fund (SRF), and on the last day of 2018 wrote two checks—one for $500,000 to Richard Huganir at Johns Hopkins and another for $300,000 to fund a research project by Gavin Rumbaugh of the Scripps Institute and Jimmy Holder of Baylor University and Texas Children’s Hospital.
Mike says his connection with the team at the Dravet Syndrome Foundation, who encouraged him to focus on funding scientific research of SynGAP1, provided the model for the launch of SRF. “I’m very comfortable saying that SRF was an unapologetic and an approved copy and paste exercise of the Dravet Syndrome Foundation.”
Once SRF provided its first grant, things developed rather quickly as other parents of kids with SynGAP1 began to “come out of the woodwork” to find out how they could help. “They were energized by SRF spending money on research and not just building something to raise awareness of the disease,” Mike says.
Soon after, he was fielding calls from companies asking him about SynGAP1. “Suddenly, we were way ahead of schedule, and we were just in year two,” Mike adds.
All the while, SynGAP1 patient families continued to become involved with SRF, and Mike understood that he was building a vibrant community of activated families who were eager to contribute in any way they could. Continuing conversations with people both in the SynGAP1 community and industry led him to add another layer to the work of the Fund. “I quickly came to understand that patient data was just as important as any research we were funding, and there was no good patient registry in our community.”
After consulting with a number of different companies, Mike chose ciitizen, a division of Invitae, to host and manage the SynGAP1 patient registry data. “They do all the data collection, get data ownership right, and their data is not a bunch of patient responses, but instead is based on medical records,” he points out. “They were a quantum leap better than the others.”
Soon after his due diligence on ciitizen, and amid getting pressure from his Scientific Advisory Board to fund a natural history study of SynGAP1, Mike signed an $80,000 contract with ciitizen to manage the data for the registry.
“I thought the patient registry was something faster [than the natural history study] and scalable,” Mike explains. “The time was right, and we then recruited aggressively.”
The recruitment also helped define, at least a bit more accurately, the total number of people diagnosed with SynGAP1 syndrome around the world. At the time Tony was diagnosed in 2018, the arms-length consensus was about 200 patients, or as many as 300. No one really knew. Tapping the SynGAP Global Network and closed social media lists, SRF’s first census, broken down by country, included 431 SynGAP patients. SRF updates these numbers quarterly and at the end of the 3rd quarter 2022, the census now counts 1,135 patients.
SRF’s fundraising has grown organically, largely through community grassroots fundraising efforts. SRF’s tax documents show that in 2019 it received $382,888 in contributions and grants. Contributions increased to $590,087 in 2020 and $1,364,391 in 2021. To honor the commitment that 100% of all money flowing into SRF goes directly to research, Mike and his wife Ashley continue to pay all administrative expenses incurred by the Fund.
Perhaps the most visible fundraiser was in 2021 when Pennsylvania YouTuber Brett Stelmaszek —himself the father of a child with SynGAP1 syndrome—wrapped his Tesla in SRF logos for a drive across the U.S. that raised more than $150,000. That money was used to contract with public benefit company Rarebase for research to screen for already approved drugs that may benefit SynGAP patients.
While SRF focuses largely on research activities, it knows that allowing parents to get reimbursed for treatments is vital. To that end, SRF dug into the CDC trenches and received an ICD-10 code for SynGAP treatment insurance reimbursement. Mike also produces a blog and has short 10-minute SynGAP1-focused podcasts aimed at providing a single resource for getting families of those newly diagnosed the information they are looking for, and further reinforces engagement.
Other efforts are ongoing at SRF and its growth into other areas, including having a patient registry, will serve to fuel further academic research and the discovery of potential treatments alike.
“We’ve moved as fast and as hard as we could to catalyze things,” Mike concludes. “Companies are well aware that having a supportive, collaborative, well organized, low drama patient group to work with, helps them get things done, and we will continue to build SRF to develop an ASO to fix it.”
The drug developer
Casey McPherson knows loss. The Austin, Texas-based singer-songwriter lost his father to mental illness and suicide when he was 18 and five years later mourned again for his brother who also committed suicide. These heart-wrenching events led Casey to serve on the boards of Mental Health Texas and Austin Child Guidance Center where he worked to raise funds and awareness of mental health issues, experiences that serve him well today.
During this time, Casey built a career as a musician, first forming the band Endochine and in 2005 the band AlphaRev which was voted the number one indie band in Texas and number 16 nationwide. And in 2011 he became the lead singer of the band Flying Colors composed of former members of the Dixie Dregs and Dream Theater.
It was amidst this backdrop that Casey’s daughter Rose was diagnosed with a rare disease, a de novo mutation in the HNRNPH2 gene that is characterized by developmental delay, intellectual disability, autism, hypotonia, and seizures.
“I’ve been a professional musician most of my life. I had zero experience or knowledge around rare disease,” Casey says. “I saw special needs kids. As artists, we’d go to Easter Seals and volunteer a day every year and play for some of those kids, which now I know were all kids with neurological diseases. But that was the extent of it.”
As Rose’s symptoms continued to emerge, Casey and his wife found themselves on the diagnostic odyssey so many parents of children with rare disease experience and realized that if they wanted answers the effort would come from them. “I saw how hard we had to work just to get a diagnosis,” he explains. “It was really her mom and I that figured out what was wrong. We got a whole-exome sequence, but it was not something the neurologist suggested.”
From his experience, Casey saw how broken the healthcare system is, especially for kids with a rare disease like his daughter who exhibit obvious signs of a deteriorating health condition, but have few avenues for a diagnosis, and virtually none for any kind treatment or a cure. But as Casey researched rare diseases, he came to find how broadly they affect people around the world. Casey, still grieving from Rose’s diagnosis then Googled the term “parent cures child of rare disease” and was flooded with article after article of the development of the drug milasen, the first N-of-1 drug ever approved by the FDA and named after the girl it was designed for—Mila Makovic.
Driven by his own desire to find a cure for Rose, Casey contacted Mila’s mom Julia Vitarello and has since developed a deep friendship with her. “She began to mentor me on the process and to connect me with people very high up in the different organizations and to expose me to the network of parent led drug development, and the scientists, researchers, foundations, and regulators who support it,” he says.
Encouraged by these connections, Casey had found the course he would take for his daughter, raising money to fund the development of a drug to treat or cure her condition. And from this, the To Cure A Rose Foundation was born.
But he was not without self-doubt.
“I was like, is this even something that I can do? I’m just a lead singer in a band. The only drugs I knew were the ones on the East Side,” he quips. Yet as he continued to dig into the world of drug development, he soon realized that, to his way of thinking, creating a new drug was not very different from the creative process of writing a new song.
“Drug development is so interesting to me, because it reminds me a lot of making a record in that there are pieces, and there are experts in each one of these pieces,” Casey explains. “The creative process of making something from nothing is full of failure. It’s full of chaos. It’s full of multiple opinions.”
What he has brought to the process though, is the creative tool of thinking outside the box. Casey says that soon after Rose’s diagnosis, he became involved with the Yellow Brick Road Foundation, a HNRNPH2 advocacy group that was raising money for a natural history study of the rare disease, but also had engaged a pharmaceutical company to begin drug research for a treatment. Soon after, he discovered that in these situations, the foundation had no control over any intellectual property from the work it was funding.
Combine this, with what seemed to be a condescending attitude from the pharma industry, and it seems natural that Casey would eventually launch his own rare disease drug discovery and development company, Everlum Bio.
“As much as I appreciate advocacy and bringing the community together, what I saw were scientists and biotech companies, patting family foundations on the head saying: ‘Keep putting those patients together. Keep getting that natural history study. Keep organizing your group, and maybe one day you’ll get lucky and we’ll make a drug for you.’ That made my blood boil,” he admits.
The Cure A Rose Foundation has always been about finding a cure to HNRNPH2, and now Everlum Bio’s mission is to provide a platform for those looking to develop drugs for other rare genetic diseases via a “lab as a service” model that provides a one-stop shop for early-stage research while also allowing organizations that use the service to retain all IP rights. “Part of the reason I wanted a lab was so I didn’t have to pay big pharma prices,” Casey notes.
The approach Casey is taking to drug development is also a bit different than the norm. “An academic approach has typically been, let’s learn everything we can about the disease, let’s find the druggable targets, and then let’s come up with the drug,” he says. “That doesn’t work when you have a kid that’s on the clock.”
To his mind, drug development for a host of rare diseases will be built around a set of customizable processes, each process owned and perfected by different organizations, that can produce a drug for each patient, or a very small number of patients. “Today, the drug is the intellectual property. I think that’s what we have to start moving away from, and see the pieces that companies can own part as part of process. It’s a service. It will be a community of companies working together with the right alignment of incentives,” he adds.
The hope is that by creating a repeatable, process-driven approach, capable of being used to create a multitude of rare disease treatments, it will open the path to creating a broad menu of rare disease treatments.
“We need to create an entirely new way to doing drug development, and approving drugs. If we can solve the rare disease equation, we can usher in personalized medicine.”
While Casey, Mike, and Effie have made their mark finding their niches in advancing the science and awareness of rare diseases, they are not alone. Countless other parents and family members have also taken up the mantle of pushing for cures, funding for research, securing payer reimbursements, and providing help to navigate the healthcare system. These tireless parents are the new face of advancement in treating rare disease and prove that there is strength in numbers. While one parent can make an impact, it’s the community of rare patients that will continue to accelerate progress in the field.