A Study Started Half a World Away May be the First Step Toward a Cure

By Sandra Bretting in Shine, a magazine of Texas Children’s Hospital

Normally, when doctors deliver a diagnosis, their next words focus on a treatment or cure. But, what do you do when there is no cure and your child is the patient?

That scenario became real for the Herndon family of The Woodlands in June. During a visit to Texas Children’s Genetics Center, they learned their 6-year-old son is not suffering from a common eye ailment, like they had originally thought, but from a rare genetic disorder called Batten disease. That diagnosis sent their lives into a tailspin.

A Typical Texas Boy

As a toddler, Will loved nothing more than to play with his toy cars for hours on end. Although he didn’t learn to speak until he was 3, his parents weren’t too concerned. In every other way, he was a healthy, normal kindergarten student.

Until last fall, when his teacher noticed Will had begun to hold his schoolbook only inches from his face in order to read the words. She told the boy’s mother, Missy, that perhaps he needed glasses. Around the same time, Missy overheard Will ask his younger brother, who was 3 at the time, a seemingly innocent question.

“What color is this crayon?” Will asked his sibling. These events began a journey through multiple eye examinations and a growing fear that something was seriously wrong with their son.

“One day I told Will to be ‘patient,’ and he asked me what I meant,” Missy recalled. “Now, Will has heard me use that word a thousand times. I could tell there were gaps in his knowledge; whole blocks of information were missing.”

After taking Will for myriad eye examinations, the Herndons ended up in the office of Richard Alan Lewis, M.D., a genetic retinal specialist at Baylor College of Medicine. It was Lewis who suspected an underlying diagnosis and recommended the Herndons bring Will to Texas Children’s Genetics Center for testing.

“It was the week Will turned 6,” Missy said. “I’ll never forget that. Dr. Lewis thought it could be one of two genetic diseases. He didn’t want me to write them down because he didn’t want me to look them up and be upset.”

“Usually I’ll diagnose about one child a year with the disease,” Lewis said. “Ironically, I’ve seen four cases alone in the last two years. The interesting thing is that the infantile strains affect babies neurologically first, while the juvenile form, such as Will’s, presents as a fairly rapid deterioration of vision first.”

Battling a Deadly Disease

Batten disease is a genetic disorder that affects the body’s nervous system. Substances called lipopigments—fats and proteins—build up in the body’s tissues and these children’s cells aren’t able to break them down or recycle them.

There are three major variants: infantile, late infantile and juvenile. Will has the juvenile form, known professionally as juvenile neuronal ceroid liopofuscinosis (JNCL).

“When the results came back as Batten, we immediately said, ‘Okay, how do we fight this?’” Wayne, Will’s father, said. “And the answer was … you don’t. There’s no cure and limited research going on right now.”

Unwilling to accept a death sentence for his child, Wayne spent countless hours each night on the Internet, finding out everything he could about the disease. Fate—or divine intervention as the couple believes—brought the Herndons together with another Texas couple who were given a diagnosis of Batten disease by Lewis.

Charlotte and Craig Benson of Austin had already formed an organization called the Beyond Batten Disease Foundation that seeks to promote research into this little-known illness. The Benson’s 7-year-old daughter, Christiane, was diagnosed with Batten disease in 2008.

The Bensons donated $500,000 through their foundation to Texas Children’s Hospital. Coupled with a $2 million donation from close friends Cherie and James Flores, the gifts were used to bring Andrea Ballabio, M.D., and a colleague from Italy to America to conduct research into neurodegenerative diseases like Batten.

A Dedicated Scientist on the Hunt

Half a world away, Ballabio had already isolated the gene that controls cells’ ability to degrade and recycle toxic molecules. As scientific director for the Telethon Institute of Genetics and Medicine in Italy, Ballabio published his findings in the July 24, 2009, issue of Science magazine.

“We discovered a novel biological mechanism by which cells degrade and recycle toxic molecules,” Ballabio said. “We also found a way to enhance this mechanism to improve cellular clearance. We hope we can use this discovery to treat neurodegenerative diseases, such as Batten, which are caused by the accumulation of toxic molecules in neuronal cells.”

Along with his colleague—Marco Sardiello, Ph.D.—Ballabio will spend a year as a visiting scientist at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. He’s also a visiting professor in the department of molecular and human genetics at Baylor College of Medicine.

The neurological research institute, which is currently under construction in the Texas Medical Center, will open next year and aims to be the preeminent research facility for pediatric neurological disorders in the country, if not the world. The goal is to give scientists, like Ballabio and Sardiello, the tools and proximity to other scientists to make the most of their research.

“It is a wonderful gift to have Dr. Ballabio working with our team,” said Huda Zoghbi, M.D., director of the Jan and Dan Duncan Neurological Research Institute. “He’s a distinguished scientist whose research epitomizes the mission of this institute.”

The Rest of the Story

Throughout the coming year, Ballabio and his team will research ways to enhance the function of master genes that regulate the efficiency of how cells clear toxic molecules.

“We are working very hard towards the application of our discovery for the cure of Batten disease, as well as other neurodegenerative diseases,” Ballabio said. “We will need time, but we hope to be successful in this difficult task.”

“We could throw ourselves into self-pity, or we could work to help find a cure,” Missy said. Recently, she joined the Blue Bird Circle, which is a group of volunteers who work with the hospital’s pediatric neurology clinic. “At some point in time every disease was without a cure. Now, it feels like it’s all coming together. I believe in my heart that these children are going to make it into adulthood.”