Scientists are one step closer to treating a rare and fatal brain disease, after one family turned their tragedy into hope for others. This ScienCentral News video has more.
A Rare Legacy
Playing catch is a simple pleasure for Lisa Van Vleck and her two sons. But a rare genetic brain disorder called vanishing white matter disease (VWM) kept her oldest son, Nathan, on the sidelines. "He loved watching people play sports," says Lisa Van Vleck from Pittsford, NY.
But now Nathan is a key player in helping researchers understand this debilitating disease. His brain cells have shown, for the first time, that the type of cells they expected to be defective are actually normal, while others, surprisingly, are not.
A very happy, social kid, Nathan's slow speech development by age two gave the first signs to both his parents and his pediatrician that something was wrong. "At first his gait was a little awkward, but he could walk — we thought he was normal," Van Vleck says. "But all the tests came back normal and everyone was just baffled. We went on for years like that."
Lisa Van Vleck
Tragically, in spite of some gains along the way, Nathan's decline was steady, confining him to a walker and then a wheelchair to get around. "It was very hard to watch," his mother recalls. "He realized it himself, he would say, 'Why can't I walk? I used to be able to walk.' And we didn't have any answers for him."
After a nearly lifelong fight with this incredibly rare inherited disease, Nathan died at age 12. The family allowed doctors to immediately sample his brain cells. "We'd do anything to help so some other child wouldn't have to suffer," says Van Vleck.
By growing and studying those cells, genetics researchers like Chris Proschel were offered an unprecedented, in-depth look at brain cells affected by VWM. Thanks to the generosity of the Van Vlecks, they are now learning how Nathan's white matter — which normally helps signals pass between brain cells (neurons) — perished from the disease.
"This was really the last shot for Nathan to contribute," says Proschel, from the University of Rochester Medical Center. "The ability to study a cell… under controlled conditions is a powerful tool."
VWM is inherited in an autosomal recessive manner, meaning that it is a disease that can run in the family. Symptoms generally appear in young children who may have been appearing to develop fairly normally. However, it has recently been shown that it can also begin at or shortly after birth, or even in adulthood.
VWM attacks cells that make up part of the brain's white matter, and while we hear a great deal about the importance of our "gray matter," the brain's white matter is also vital to our health. Our white matter is mostly made up of glial cells that form a myelin sheath that protects and insulates the connections between the brain's nerve cells, helping them to receive and interpret messages from the brain at maximum speed. Currently there is no treatment for the loss of myelin that results in VWM.
The gene responsible for the disease was pinpointed by a group led by Marjo van der Knapp in 2001, but it is unclear how the defect causes the disease. Teams like Proschel's are working to understand, at the cellular level, exactly how a defect in the gene may lead to the massive disruption of myelin, which is thought to cause the symptoms of VWM.
"Since we expected these myelin-producing cells to be sick, that's where we started looking," says Proschel. But, he explains, they actually found these cells to be normal. "To our surprise we found that quite a significant amount of myelin producing cells were there."
Star-shaped astrocyte image: Chris Proschel, University of Rochester Medical Center
In fact, a totally different part of Nathan's white matter — star-shaped cells called astrocytes — failed to grow normally.
Astrocytes were long thought of as simply support cells for neurons, but in recent years scientists have been discovering how crucial they are for overall brain health. "In many lesions where the brain is affected by trauma, these cells become very active and prominent because, we assume, they play a role in the repair process," Proschel explains. "These cells were not as numerous as we expected, and those that were there did not look like normal astrocytes. "
Proschel says this discovery will be crucial to ever treating or curing the disease. "If you're going to try to replace cells, you have to know which cells you're replacing… we need to include these star-like astrocytes along with the myelin producing cells."
The investigation not only yielded important knowledge about how the disease affects the brain, but it also marks one of the first times that scientists have been able to isolate neural stem cells from a patient and use them to learn what is going wrong in the brain of a patient with a complex neurological disease.Proschel believes that the techniques used to study Nathan's white matter will also help in developing treatments for other genetic illnesses. "[Nathan] led us onto the right track, and hopefully has pointed us in a direction that will allow us to find answers that will let us find a therapy sooner than if we had continued with our previous assumptions," says Proschel.
The discovery has also given comfort to Nathan's family. "His life made a big impact on what's going to happen in the future, so I feel like there's a reason for all of this," Van Vleck says.
So while the Van Vlecks are missing their cheerleader, they know a little bit of Nathan lives on.