Taylor King was nearly 8 years old — a runner, who loved pink and wearing dresses — when she was diagnosed with infantile Batten disease in July 2006. By that October, her family had started fundraising for a cure.
“At the beginning, there was a huge groundswell of support in the local community in Charlotte, North Carolina,” said Laura King Edwards, co-founder of the foundation Taylor’s Tale, and Taylor’s older sister, in an interview with Batten Disease News. “There was a palpable sense of hope that what we were doing could save Taylor’s life, and that was a huge driver for fundraising early on.”
To date, Taylor’s Tale has raised $1 million for research about Taylor’s form of Batten disease, caused by a mutation to the CLN1 gene. “As the years went on, our community and friends have continued to support our efforts, but we’ve also had to get a bit more creative,” Edwards said. “The net we cast has expanded.”
Batten is a rare and devastating neurodegenerative disease, caused by mutations to the genes controlling the systems that cells use to clear out waste material. Without a functioning disposal system, bits of protein and fat build up in cells in the brain and throughout the body, causing them to deteriorate. The gradual breakdown of cells in the nervous system leads to seizures, vision loss, and a gradual decline in cognitive function.
There are multiple forms of Batten, marked by different genetic mutations, different ages of onset, and different life expectancies. A CLN2 mutation, causing late-infantile Batten, for example, strikes in early childhood, and children rarely live to their teens. The juvenile form of the disease, resulting from a mutated CLN3 gene, first shows its symptoms at ages 4 to 7.
Though symptoms are similar, and day-to-day challenges often overlap, each form of Batten requires its own treatment, which is why fighting the disease across the board can be challenging.
A limited amount of funding for rare diseases like Batten is available from the National Institute of Health (NIH), which funds a large share of the basic biomedical research in the United States. What funding is available is divided among 7,000 or so rare diseases — then subdivided among a disease’s subtypes. That ever-smaller pot often leaves families of patients like Taylor with the task of raising awareness, advocating research, and funding potential therapies.
Many families choose to form small and single-focus foundations, hoping to find a path forward.
“In these cases, advocacy almost plays a stronger role than the science does,” Steven Gray, PhD, said in a phone interview. Gray is an associate professor of neurology and pediatrics at UT Southwestern Medical Center who works on Batten disease research funded by Taylor’s Tale.
When Taylor’s family and friends first started raising money for Batten, they worked with the Batten Disease Support and Research Association (BDSRA), the largest Batten group in North America. BDSRA has chapters and members across the globe, and each year fields calls from about 30 different countries.
“This organization started 30 years ago when parents, who had no other way to connect, wanted to reduce that isolation and then gather resources to get researchers started,” Margie Frazier, executive director at BDSRA, said in a phone interview. The organization has raised about $7 million for Batten disease research since its founding, and leveraged that amount to generate an additional $7 million for Batten from the NIH and other groups, Frazier said.
BDSRA tackles all forms of the disease. “Our mission is to end Batten,” Frazier said. “We need to be a go-to for all of the forms … there are so many cross-cutting issues, not just with the science, but with the support the families need.”
From its vantage point overlooking the landscape of Batten, BDSRA has funded patient registries, animal models of disease, and gene discovery projects. “We know that people who enter the Batten space will need those tools,” Frazier said. “They’re assets to a research community that all groups have access to.”
Unlike BDSRA, most of the small foundations centered around individual patients, like Taylor’s Tale, focus on just one form of Batten — the form that particular child has. BDSRA often provides information and support to those targeted groups, Frazier said, and helps connect them with scientists.
Taylor’s Tale, for example, started off raising funds for BDSRA, before breaking off to form its own foundation after about two years. “It seemed like the best opportunity for us to make an impact,” Edwards said.
Gray has received research funding both from BDSRA and individual family foundations. “It’s an interesting dynamic,” he said. “Individual families, who do the bulk of fundraising, they’re going to want to see their disease treated, so they look to fund that directly.”
The foundations, though, often remain connected to BDSRA. “We continue to work closely with BDSRA,” Edwards said. “They’re an incredibly important part of the Batten community. We always worked with them closely to identify fundraising targets, and projects that we should fund with the money we raise.”
One of BDSRA’s roles, Frazier said, is to partner with groups like Taylor’s Tale as they raise money and move potential treatments for Batten forward in the research process. That is done by making introductions to researchers and pharmaceutical companies, providing small research grants to bridge projects, assisting families who participate in clinical trials, and accompanying groups to the U.S. Food and Drug Administration (FDA) as they push for drug approvals.
Though BDSRA facilitated and worked behind the scenes of the many research advances in Batten over the past decade, most of the heavy lifting, financially, came from the efforts of individual foundations targeting specific forms of the disease.
Gene therapy for the CLN2 form of Batten is in a second round of clinical trials (NCT01414985) at Weill Cornell Medicine, largely due to the fundraising efforts of the foundation Nathan’s Battle. Nathan Milto, the foundation’s namesake, and his brother, PJ, participated in the first round of the trial.
“If it wasn’t for Phil Milto [Nathans’ father], we’d never have gotten started,” said Ron Crystal, MD, who leads the project, in a phone interview with Batten Disease News from Weill Cornell in New York City. “He deserves a huge amount of credit. I’ve been doing this for a long time, and I’m always impressed by the families, and how individuals can make a real change.”
Another gene therapy, under investigation for the CLN6 mutation, was funded primarily by the Charlotte and Gwenyth Gray Foundation to Cure Batten Disease. The girls’ father, Gordon Gray, is a producer, known for work on sports movies like “Miracle” and “The Rookie.” After both Charlotte and Gwenyth were diagnosed with the CLN6 form of Batten, Gordon was able to call on stars like Rhianna, Channing Tatum, and Jessica Alba to help raise awareness and bring in donations.
“In the first week, did a social media push, and raised $1 million,” said Kristen Gray, the girls’ mother and foundation co-founder, in a phone interview from Los Angeles, where the family lives. “We were like a thoroughbred out of the gate and then, as things settled in, had to get creative about fundraising.”
The therapy is in an ongoing, open-label and single dose clinical trial (NCT02725580), expected to conclude in 2019, led by Jerry Mendell, MD, at Nationwide Children’s Hospital in Ohio. Both Charlotte and Gwenyth are enrolled in the trial; they received the therapy in 2016. In April, they’ll travel to the hospital for their final follow-up appointment, Gray said.
Taylor’s Tale, along with other family foundations and BDSRA, funded Steven Gray’s work on gene therapy for CLN1. Working with money from foundations, he said, makes the research more personal. “It’s motivating,” Gray said. “The challenge is, it’s a family trying to raise money, and things get expensive. You’re trying to do twice as much work with half as much.”
Abeona Therapeutics recently acquired Dr. Gray’s CLN1 therapy, ABO-202, and is working to move it to a clinical trial. The company hopes to continue to cultivate relationships with patients and advocacy groups in the Batten community as it develops the treatment, Jeff Davis, Abeona’s chief operating officer, said in an interview. “It’s important to have their voices heard,” he said. “They have a lot of intelligence on the disease.” They’re also helpful during meetings at the FDA, which wants to hear from patients as therapies move toward approval, Davis said.
Gray works on the CLN5 and CLN7 forms of Batten, as well as CLN1. A CLN5 gene therapy, he said, is coming along well. But progress is slow, because there aren’t strong patient advocates for this disease type. “With CLN7, we’re fairly early scientifically, but a couple families have been very committed to accelerating work,” he said.
The Beyond Batten Disease Foundation, which focuses on the CLN3 form of the disease, is one year into a two-year campaign to raise $6 million to bring its therapy to a clinical trial. To date, it has raised just less than $3.7 million. That’s an ambitious goal, said Mary Beth Kiser, president of the foundation, in a phone conversation from its Austin, Texas, offices. “In the first 10 years we were around, we raised $10 million. Now, we’re trying to raise $6 million in two years,” she said.
Beyond Batten was founded by Charlotte and Craig Benson when their daughter, Christiane, was diagnosed in 2008. Craig Benson was the CEO of Rules-Based Medicine, a life sciences company, and knew the challenges of research and development in a rare disease space, said Kiser. The foundation was created based on Benson’s expertise, with a full-time scientific advisor and a strategic plan for innovation and development.
The foundation leverages support from the communities around families with the CLN3 form of Batten. Different funds within the foundation are built around individual patients, allowing for both personal branding and contributions to larger goals, Kiser said.
“What we try to be is an umbrella. Families are interested in fundraising, and we have all the infrastructure,” she said. “There are many families who fundraise and don’t have a fund. But for those who want that, their child is front and center. It’s good model that works.”
No one else to hear, ‘nothing we can do’
It’s rare that a research project is entirely funded, from start to finish, by foundations, Frazier said. Scientists often use the initial progress made possible by foundation grants to pull in other funding from the National Institutes of Health or other sources. “Groups like ours and family foundations, they often serve as amazing startups,” she said.
Once specific projects move out from under the foundations, those groups continue to fundraise.
“Just because the trial is over for our children doesn’t mean it’s over for us as a family,” Kristen Gray said. The Charlotte and Gwenyth Gray Foundation continues to raise money, explore potential therapies, and provide financial assistance to other families dealing with Batten. Its next major goal, she said, is to open a school in Los Angeles, California, for children with neurological disorders.
Despite reaching the milestone goal of pushing a viable treatment forward, Taylor’s Tale also keeps working, Edwards said. “We didn’t stop funding breast cancer research because one treatment was out there,” she said. “Science is always improving.”
Next, Taylor’s Tale hopes to raise $175,000 to create a standard of care for clinicians to use while treating kids with CLN1 mutations. “It’s the perfect next step,” Edwards said. “We still have to manage quality of life, and there’s currently nothing for doctors and healthcare providers to lean on.”
For the group, each new milestone is bittersweet: Taylor is 19 years old now, older than most CLN1 patients. But her disease is too advanced to participate in Abeona’s upcoming clinical trial for ABO-202, the CLN1 gene therapy, and probably won’t be able to benefit from any standard-of-care protocols that are developed.
“Almost selfishly, we started this because we wanted to save Taylor,” Edwards said. “We’ve known for a long time that that won’t be possible, but we haven’t stopped. I don’t ever want there to be another family like ours that is told that there’s nothing we can do.”