Parents of Grand Forks girl fighting rare disease push for FDA approval of gene therapy that could save her life

At the tender age of 3, Daphne Enger, was a spunky, sassy, happy child. Then, one night in February 2019, the world as she and her family knew it turned upside down.

At home, Daphne had started to crawl up some stairs to the upper level where her parents, Lindsey and Brice, were. A sudden seizure left her sprawled across the first step.

At first Lindsey and Brice thought Daphne was simply exhausted from a fun day of playing and had fallen asleep in mid-crawl on the stairs. As they got closer to pick her up, they realized to their horror that she was acting differently than she ever had.

“Her body was convulsing, she was turning blue from lack of air to the lungs, and her eyes had more fear in them than anything (we) had ever seen before,” Lindsey wrote in a post on the website Caring Bridge.

The incident was the initial indication that something was seriously wrong, but it gave scant warning of the terrifying reality that was to envelop them.

A call to 911 and a trip to the emergency room confirmed Daphne had suffered a seizure – the first of many more frightening seizures, more ER visits, more hard falls to the ground, more tremors and body shakes, “more fear-filled eyes,” Lindsey said. And “many more questions with unknown answers.”

In July 2019, after a consultation with doctors and genetic testing at the Minnesota Epilepsy Group, Lindsey and Brice received the “worse-case scenario answer” that had eluded them for months: Daphne has Batten Disease-CLN2, a rare disease wherein her brain doesn’t produce an important enzyme needed for proper brain function.

They were told that every motor skill Daphne had acquired in her three years of life – along with her ability to dance and play, run and walk – would be taken from her. The disease would claim her ability to breathe and, eventually, her life.

“We were told, as fact ... your child is going to deteriorate and die,” Lindsey said.

Children diagnosed with this genetic disease have a life expectancy of 8 to 12 years.

“So we mourned the beautiful, fun, loving, sassy girl that we were still able to see, hold and talk to,” Lindsey said. “To mourn a child still alive is a situation I can’t describe.

“We gave ourselves two days to cry,” she said. “After two days passed with us crying and holding the child we were told would be taken from us very soon in the years to come,” she and Brice set out to learn what they could do “here and now” to give her the best possible life and to fight the brutal prognosis.

They immediately made arrangements for Daphne to undergo surgery to implant a port in her brain to begin the enzyme replacement treatment that slows the deterioration.

For nearly half her life, Daphne, now 6, has been battling the cruel neurodegenerative, or brain, disease that steadily steals from her. While other young children “are gaining words, skills, talents and abilities, Daphne loses these things” at a heart-breaking rate, Lindsey said.

Every two weeks, she receives an enzyme-replacement treatment, approved by the FDA in 2017, to slow the disease progression.

Daphne undergoes the treatment by Altru doctors and nurses who have been specially trained to administer it. The procedure, which takes nearly five hours, delivers the drug Brineura to the brain via a port. Brineura is a synthetic form of the enzyme that her brain does not produce.

“If she didn’t have this treatment, she would die,” Lindsey said.

Brineura is a “huge blessing” that slows deterioration of several functions but does not affect the deterioration that starts in the retina of the eye, she said.

“(Daphne) doesn’t walk very well. She has lost most of her words, and she is beginning to lose her sight,” Lindsey said. “Time is not on her side.”

Daphne has regressed developmentally, from a 3-year-old to a 1-year-old.

The treatment gives the Enger family, including Daphne’s brother Oliver, 9, “the gift of time to be with our daughter and more time for a cure to be found,” Lindsey said.

“And so Daphne fights. She has been fighting every single day for two and a half years. She has lost (so much), she fights with everything she has every minute of every day not to lose more. I am in awe of how strong she is.”

“Through it all, she keeps her smile – her smile and her sass,” Lindsey said. As the parents of “such a brave and strong girl, we are in awe of her resilience and determination.”

The Engers and other parents around the country who are facing this same terrible situation are worried that FDA officials harbor a “misconception” that the drug Brineura “is helping more than it is,” Lindsey said. “It slows the deterioration, but you have to understand how fast this disease progresses. (The drug) is not able to slow it enough.”

Children with the disease “are still deteriorating at a very fast rate,” said Lindsey, who is part of a 200-member worldwide Facebook group of parents and others who have been impacted by the disease.

These parents have started a petition and are determined to gather as many signatures as possible to urge the FDA to look carefully at the positive pre-clinical trial results of gene therapy for Batten Disease and approve clinical trials.

The gene therapy would alter Daphne’s genes to make her brain develop the enzyme it needs for proper brain function. The therapy has been shown to be effective in not only stopping disease progression, but restoring the functions that have been lost, Lindsey said.

Results of preclinical trials have been “100% successful – that really gets us going,” she said.

These parents want the FDA to “fast track” the therapy, she said. “We know they can fast track it.” And they believe that, given the impact of the petition signatures, the FDA will be persuaded to quickly move the gene therapy forward.

“We understand the rarity of the (Batten) disease,” and that there are many worthy causes, Lindsey said, but “we are not grasping at straws.”

“We need the FDA to see that these children’s lives have potential, they have meaning,” she said. “(These children) have the right to live the same full and long life everyone else is promised. These children, including Daphne, deserve to live.”

“We need to give our children every possible chance to save their lives,” she said, noting that companies working on the therapies “are ready to go.”

If the FDA approves clinical trials, it would give hope to many others who are afflicted with Batten Disease.

If trials are approved, she and Daphne are ready at a moment’s notice to go wherever they must – out of state or out of country – to participate.

“We are almost at the finish line,” she said. “We just need to get the FDA’s attention now.”

Dealing with this crisis “has been really hard,” Lindsey said. “It has changed us; it’s made us stronger. We have a lot of faith, a lot of hope, a lot of love.”

“We have not and will not give up hope and faith for a cure for Daphne before it is too late,” she said, adding that her daughter is “inspirational.”

“She’s so happy all the time,” Lindsey said. “I don’t want to lose that smile, that laughter.”

To sign a petition that urges the FDA to approve gene therapies for children with Batten Disease, go to https://chng.it/wRZjqXZk9G , and share it with others to sign, “so we can get the attention of the FDA please and save our children,” said Lindsey Enger. “You don’t have to donate. We just ask that you please sign the petition and share it for Daphne.”