Colorado family raising money to treat rare FRRS1L gene disorder

At first, Everly Green’s parents didn’t understand why her doctors wanted genetic testing. Their daughter was behind on her milestones at 18 months, but was gradually making progress, and they expected that to continue.

Then, when she turned 2, the seizures started. She suddenly began to lose skills. Three months later, Everly needed a feeding tube. Now, at 8, she can only move her eyes, allowing her to communicate via a screen.

Everly, whose family lives in Fort Collins, has a rare mutation in a gene called FRRS1L, pronounced “frizzle,” which affects how cells in her brain communicate. Her parents, and other members of the tiny community of children with the condition, have worked with researchers and small-scale manufacturers to develop a treatment that could restore some of her ability to move — but only if they can raise $4 million to develop and test it.

Everly clearly understands what happens around her and loves school, where she learns in a mainstream classroom with support and has several best friends, said Chrissy Green, Everly’s mother. Still, she wants to do things she can’t, such as holding toys on her own or going on the occasional family trip with her brothers, Green said.

“These kids are in there, they want to play like other kids, they just can’t move,” she said.

Green is co-president of the foundation Finding Hope for FRRS1L, which is collecting funds for the next stage of drug development. Children with FRRS1L gene disorder, the foundation’s website says, “are trapped in a body they can’t move, however still retain high cognitive function, understanding, communication and awareness.”

Worldwide, only a few dozen children currently have a diagnosis of the same mutation in FRRS1L, meaning there’s little interest from drug companies. Families are on their own to fund research and, if all goes well, convince the U.S. Food and Drug Administration that the treatment is safe and effective enough to go on the market.

And, even if they succeed with the FDA, they’ll still face a battle with insurance companies that may not want to pay the steep price for a drug to correct a faulty gene. (Even though the families aren’t looking to make a profit, these types of treatments are expensive, and the company under contract to do the manufacturing isn’t doing it for free.)

Gene therapy involves replacing a faulty gene with a healthy one, usually via a harmless virus engineered to insert a specific snippet of genetic code. It has offered a new way to treat infants born without functioning immune systems, who previously relied on bone marrow transplants. Trials have also shown good results with a liver problem causing ammonia to build up in the body, and one form of inherited deafness.

The technology also carries risks. Patients have died after receiving gene therapies, with liver problems emerging as a potential risk.

Normally, drug companies take on the financial risk of turning basic research that’s often publicly funded into treatments, with the hope of eventually making a profit. For gene therapies, that model can break down because of the small number of patients. Green’s FRRS1L foundation knows of about three dozen patients worldwide, though other children with unexplained seizures could have the mutation.

A drug that treats so few patients will never be profitable, so parents are largely on their own in trying to fund research and development, said Neil Hackett, a researcher who has worked with families on gene therapies and advised the FRRS1L foundation. Usually, they can’t do it unless they happen to have one or more business-savvy parents with the time and resources to run a foundation while caring for a child with complex needs, he said.

“They need specific expertise, which is not easy to find, and they need massive amounts of money,” he said.

When they first received Everly’s diagnosis, her doctor told the family to make the most of the time they had left, because medicine couldn’t offer anything to extend her life or reduce her symptoms, Green said. She didn’t initially question that, but focused on loving her daughter and trading tips for daily life with other families via Facebook.

Green connected with a mother in London who had a child the same age as Everly. Viviana Rodriguez was exploring whether researchers had found any evidence to suggest they could repurpose existing drugs to reduce FRRS1L symptoms.

Through a “providential” series of events, one of Rodriguez’s contacts knew a doctor at the University of Texas Southwestern Medical Center who worked on gene therapies. That doctor had read a paper from a German researcher who bred mice with the FRSS1L mutation so he could study it. The German scientist had given the mice a gene therapy as part of his experiments, but his work wasn’t focused on the clinical applications, Green said.

Green and Rodriguez, along with a small group of other parents, formed the foundation to raise $400,000 for the UT Southwestern researchers to breed their own group of FRSS1L mice and give them a gene therapy in a study that was set up to show results. The mice that received the gene therapy had near-normal movement after it took effect, she said.

“We saw major recovery in the animals, so we’re really hopeful for our kids,” she said.

The next step was testing for toxic side effects, then finding a manufacturer who could do the complicated work of inserting the corrected gene into a harmless virus, Green said. If they can raise the necessary money and all goes as expected, children could receive their doses through a clinical trial starting in September, she said.