Story, Patient, Research and Innovation

Healing Kids Precisely

May 5, 2023

From testing to diagnosis to treatment, precision medicine transforms care for kids with rare neurodegenerative condition.

A young boy surrounded by adults inspects something in his hand

At 5-year-old Connor’s appointment in the Neurogenetic Pediatric Clinic, Scott Demarest, MD, holds pieces of cereal in his palm. Dr. Demarest, a neurologist and the clinical director for the Children’s Hospital Colorado Precision Medicine Institute, gently coaxes the hungry little boy into using each of his hands – right, then left – to pick up these small bits of food, testing Connor’s fine motor skills.

For Connor, who has Batten disease, a rare neurodegenerative condition that affects the brain, vision and muscle control, the pincer grasping motion can be challenging. It requires precision and coordination – just like the medicine and care that make it possible for the pre-kindergartener to perform this task.

Precision medicine advances care for rare disease with no cure

Batten disease was first described by Dr. Frederik Batten in the early 1900s. Nearly 100 years later, human genome sequencing allowed scientists to identify the genes responsible for this devastating condition. Today through genomic research, scientists know that more than 400 mutations on 13 different genes, labeled “ceroid lipofucinosis, neuronal” (CLN) genes, interact in a complex way to cause the 13 subtypes of pediatric Batten disease.  

These CLN genes provide instructions to cells to make an enzyme that essentially serves as the brain’s garbage collector. Without this enzyme, waste builds up in the brain’s cells – and the cells eventually die. Batten disease, which is fatal, is believed to affect about 14,000 kids worldwide, including several hundred children in the U.S. Currently, the disease does not have a cure, and only one form of Batten disease – CLN2, Connor’s type – has an FDA-approved therapy.

Children with this condition often appear to be developing normally as babies and toddlers, but around age 3, the first signs of Batten disease typically start to appear. By the time most kids exhibit symptoms, they have already sustained serious damage to their brains and have begun losing the ability to do very basic functions, such as walk, talk and see. They’ve also likely had one or more seizures, which can cause significant harm and are often misdiagnosed as epilepsy of unknown origins, without identifying the underlying cause of the seizures.

That was the case for Dylan, now 7, another Batten disease patient who receives care at Children’s Colorado. Dylan’s mom, Michelle, said it took more than a year for the little boy, whose family lives in rural Nebraska, to be accurately diagnosed through genetic testing and to begin receiving treatment. During the year in which Dylan’s condition went undiagnosed at other hospitals and clinics, his health rapidly deteriorated, causing irreversible damage to his brain and body.

Precision medicine is beginning to change all of this. There is new hope for kids with Batten disease, thanks to earlier genomic testing, better and faster diagnoses, and a relatively new, innovative enzyme replacement therapy, called cerliponase alpha, discovered through precision medicine research.

For four young boys being treated at Children’s Colorado, including Connor, Dylan, and brothers Damion and Adriel, cerliponase alpha is slowing the neurodegeneration normally seen with their disease, not only extending their life expectancies, but enhancing the quality of their lives. Since Damion, now 11, was diagnosed with Batten disease, doctors screened his younger brother, Adriel, as a baby and diagnosed him with the same condition. Adriel started receiving cerliponase alpha at just 4 months old, before his symptoms even began, making him the youngest patient in the world to receive this therapy. He is now 15 months old, and Children’s Colorado doctors are hopeful that the onset of his Batten disease can be delayed significantly, perhaps even in time for a cure to be developed.

“Cerliponase alpha has completely altered the progression of CLN2 Batten disease,” said Dr. Demarest. “It is a complicated treatment to administer every two weeks directly into the fluid around the brain in four-hour infusions, but it has given hope and time back to CLN2 patients and families. Although this is one of the most complicated drugs there is to provide, it is also one of the most rewarding.”

The power of an early diagnosis

When Connor was born, he seemed like a healthy baby. Then, several months after the red-headed, blue-eyed boy’s second birthday, Stephanie and Brian, Connor’s parents, started noticing developmental delays and impairments in his speech, vision and memory. And in December 2020, just one month before Connor’s third birthday, “everything came crashing down,” said Stephanie.

While she was driving, Connor had a seizure in his car seat. He stopped breathing and turned blue. Connor had multiple seizures in the weeks that followed. The couple took their toddler to Children’s Colorado, where doctors quickly recommended genetic testing. Just 10 days later – and only 8 weeks after the little boy’s first neurologic episode – the couple learned that Connor had late infantile Batten disease, also known as CLN2. They were in Dr. Demarest’s office the next day. And one week later, Connor underwent surgery to install a shunt in his brain to provide a port for cerliponase alpha infusions, which replenish the critical enzyme the little boy’s body does not produce.

Connor was diagnosed much faster and earlier than many other kids with Batten disease and received therapy much more quickly as a result. Because of this, he does not exhibit nearly as many of the signs of his disease as would otherwise be expected; he is still walking, talking, climbing up on things and riding a bike. His seizures are much more infrequent and controlled.

“Connor is a true testament to the power of early diagnosis,” said Taylor Schwab, the neurology complex drugs team’s clinical specialty coordinator, a highly skilled role among the multidisciplinary caregivers serving Connor, responsible for coordinating schedules and many aspects of the infusion process. “I really hope that’s what we will see if younger and younger kids can be diagnosed and receive enzyme replacement therapy before they have any symptoms.”

Donors make precision medicine advancements possible

Due to the costs of genetic testing and the complexity of delivering medications like cerliponase alpha to patients, philanthropy plays a significant role in improving access to testing, the development of innovative therapies and better outcomes.

When donors give to our Precision Medicine Institute, they help ensure that more kids and families get the genetic testing they need and that new treatments can be discovered. And philanthropy can also help support unique positions like our nurse clinical specialty coordinators, who orchestrate the multifaceted care and medication administration that children and families need. “These roles are irreplaceable in my opinion,” said Michelle, Dylan’s mom.

“The impact of donors giving to these areas is huge,” said Stephanie, Connor’s mom. “It totally changes the quality of life for a child and their family. And it provides hope. I remember our diagnosis day, and if the next sentence after learning about this disease hadn’t been, ‘There’s a treatment, it’s available, and you can start next week,’ I would have been a puddle on the floor. Instead, I got to have hope because there is a treatment for my son’s rare disease. That means more play with his peers, more time doing the things he loves, more life and more time with us – isn’t that what we all want for our children?”