A disease with no cure and the family trying to find one

Josh and Laura Ledbetter, of Ooltewah, Tenn., a suburb of Chattanooga, pictured with their sons Grayson, 5, and Cooper, 9. Photo / Rebecca Helton - Washington Post

Laura and Josh Ledbetter know they have only a few years left, at most, until their 5-year-old son, Grayson, dies.

A year ago, Grayson was diagnosed with Alexander disease, an extremely rare type of leukodystrophy that destroys the white matter that protects the nerve fibres in the brain, resulting in debilitating mental and physical delays and, in most cases, death by age 10.

It's a disease so rare only about 500 cases have been reported since 1949.

The Ledbetters, who live in Ooltewah, a suburb of Chattanooga, Tennessee, had never heard of Alexander disease before Grayson was born. Now they are part of a small community of families trying to figure out what they can do for their children who have no hope of a cure.

As a baby, Grayson had trouble feeding, then learning to walk, then speaking. Doctors couldn't figure out what was behind these symptoms. At age 4, he had his first seizure, triggered by a high fever. Emergency room doctors ran a CT scan and found an abnormality. Two days later Grayson had an MRI. The results 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 Ledbetter says.

A search for specialists eventually took the family to the Leukodystrophy Centre at the Children's Hospital of Philadelphia (CHOP). Grayson, they were told, had Alexander disease. The MRI had shown deterioration of the white matter in his brain.

"I felt utterly hopeless," says Josh Ledbetter.

Gradually, Josh, an account executive for a software company, and Laura, an administrator for a cardiothoracic surgery practice, began to come to terms with the diagnosis. They enrolled Grayson in a study of Alexander disease, they created a nonprofit organisation to raise money for research, and they try to enjoy every day they have together.

"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 is part of an Alexander disease study led by Amy Waldman, a paediatric neurologist and director of the Leukodystrophy Centre at CHOP. The study monitors how the disease affects patients, gathering information in an effort to develop treatment.

Other research is under way at the University of Wisconsin at Madison, where Albee Messing, a professor emeritus of comparative biosciences, 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 recognised 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 distinctive. And so I realised that this mouse provided a clue into a potential genetic basis for the disease."

Messing and his team have 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 the oligos into mouse brains, levels of GFAP dropped dropped almost completely, offering hope that the technique could someday be used in humans.

The Ledbetters started the nonprofit Grayson's Ladder to raise funds for Waldman's study and for further research. They recently had their first fundraising event at their home, attended by four other families who have children with the disease. The families included Jennifer and Christopher Bonsky from Ohio, whose daughter Elise was diagnosed with Alexander disease in 2014. They run a nonprofit group called Elise's Corner.

Brandon and Qwynn White from Knoxville, Tennessee, also attended the Ledbetters' event. Their young daughter, Meris, was just diagnosed in November of last year. And then there's Charla Bruns from Texas, whose son was diagnosed when he was 4. Cameron has been living with Alexander disease for 16 years.

So far, Grayson's Ladder has raised nearly $100,000.

"For us who are so close to it, it's about investing in Alexander disease," says Waldman, who was a speaker at the fundraiser, "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, are trying to keep Grayson healthy. Weekdays he receives physical, speech and occupational therapy as part of his school schedule. Outside school, he goes to gymnastics to help with his flexibility, and does hippotherapy - a type of neuromuscular therapy that uses horseback riding to help improve posture and coordination.

The Ledbetters know a cure may be far off, and Alexander disease casts a dark shadow, but they live by a steadying motto. "Today is a good day."