Laura and Josh Ledbetter know they have only a few years at the most until their 5-year-old son, Grayson, dies.
A year ago, Grayson was diagnosed with Alexander disease, type of leukodystrophy that destroys white matter that protects nerve fibers in the brain, causing debilitating mental and physical delays, and in most cases, death by age 10.
It’s so rare that only about 500 cases have been reported since 1949.
The Ledbetters, who live in a suburb of Chattanooga, Tenn., had never heard of the disease before Grayson was born. Now they are part of a small community of families trying to help their children, who have no hope of cure.
As a baby, Grayson had trouble feeding, then learning to walk, then speaking. Doctors couldn’t figure out what was causing it. At age 4, he had his first seizure, triggered by a high fever. Emergency room doctors ran a CT scan and found an abnormality. An MRI puzzled doctors, who didn’t know what to tell the parents. “They wouldn’t give us results because radiologists were calling each other across the Southeast,” Laura says.
A search for specialists eventually took them to the Leukodystrophy Center at the Children’s Hospital of Philadelphia (CHOP), where they got the diagnosis
“I felt utterly hopeless,” says Josh.
Gradually, Josh, an account executive for a software company, and Laura, an administrator for a cardiothoracic surgery practice, came to terms with the it. They enrolled Grayson in a study of Alexander disease, created a nonprofit organization to raise money for research, and they try to enjoy every day together.
“I mean, Grayson, he lights up a room,” Laura says. “I don’t know that there’s anybody who wakes up happier than Grayson. He’s just the happiest little guy and always full of joy. And he’s working all day. He doesn’t necessarily know it, but he’s working and being evaluated and measured all day long. … I don’t know a 5-year-old that works harder than him.”
Grayson’s Alexander disease study is led by Amy Waldman, a pediatric neurologist and director of the Leukodystrophy Center at CHOP. The study monitors how the disease affects patients, and gathers information in an effort to develop treatment.
Albee Messing, a professor emeritus of comparative biosciences at the University of Wisconsin at Madison, also has been studying Alexander disease for more than 20 years.
“I was spending most of my time with mouse genetics and basically engineering mice, to study cell biology and development in the nervous system,” Messing says. “At some point in the mid-1990s, we created a mouse, which to our surprise, had lesions in its brain that I recognized as reminiscent of Alexander disease. And I knew about Alexander disease from my neuropathology training. … Even though it’s an extremely rare disease, it’s so distinctive. And so I realized that this mouse provided a clue into a potential genetic basis for the disease.”
Messing and his team connected Alexander disease to a protein called GFAP — glial fibrillary acidic protein. For more than a decade, they have been working on ways to reduce levels of GFAPs in mice.
About four years ago, working with scientists from Ionis Pharmaceuticals, they began using oligonucleotides, called oligos. After injecting them into mouse brains, levels of GFAP dropped almost completely, offering hope the technique could someday be used in humans.
The Ledbetters’ nonprofit, called Grayson’s Ladder, has raised nearly $100,000 for Waldman’s study and further research.
“For us who are so close to it, it’s about investing in Alexander disease,” says Waldman, “but I think for the world at large, it’s about investing in the technology that, if it’s perfected in one disease, can translate into all kinds of other diseases.”
While working toward a cure the Ledbetters, who also have a 9-year-old son named Cooper, try to keep Grayson healthy. Weekdays he receives physical, speech and occupational therapy in his school schedule. Then he goes to gymnastics to help his flexibility, and does hippotherapy — neuromuscular therapy on horseback to improve posture and coordination.
The Ledbetters know a cure may be far off, but they live by a steadying motto. “Today is a good day.”