A family's bravery and generosity in the face of their son's death three years ago has enabled researchers to make an important new finding about the brain and its stem cells.
On May 7, 2002, 12-year-old Nathan Van Vleck of Pittsford died after a nearly lifelong fight with an exceedingly rare inherited disease known as vanishing white matter (VWM) disease. As Nathan's illness progressed, the family discussed how it might help other families and patients coping with VWM, and the family decided to allow the study of some of Nathan's brain cells for research purposes. Immediately upon his death in the hospital, a team of neuropathologists and neurobiologists worked through the night to isolate some of Nathan's brain cells, which were then grown and studied in the laboratory.
The outcome was an unprecedented in-depth look at the brain cells of a VWM patient. 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. The team of scientists from the University of Rochester Medical Center reported its results in the March issue of the prestigious research journal Nature Medicine.
"This family's generosity resulted in a great study and tremendous new findings about the brain," says his physician, pediatric neurologist Carlos Torres, M.D. of Golisano Children's Hospital at Strong, the children's hospital affiliated with the medical center. "It's a great example of how a family can contribute to advances in medicine."
VWM targets cells that make up part of the brain's white matter, turning the normally strong and durable substance into a yellowish, gelatin-like material. While we hear a great deal about the importance of our "gray matter," a term that refers to crucial brain cells known as neurons, the brain's white matter is also vital to our health. Our white matter is mostly made up of glial cells that insulate the connections between neurons. In VWM, as the white matter gradually disappears, a child typically has trouble talking and walking. As the disease progresses over several years the child has seizures, goes into a coma and often dies before reaching teen-age years. Currently there is no treatment.
In Nathan's case, slow speech development around the age of two was one of the first symptoms, according to his parents, Lawrence and Lisa Van Vleck of Pittsford. Soon after, his gait became awkward, and he turned to a walker and then a wheelchair to get around as he pursued his interests, which included watching ice-skating, basketball games, and the cheerleaders, his mom says. Eventually Nathan ended up in a coma and died of the disease.
During the years that Torres treated Nathan, research at the medical center was growing dramatically. The new scientists recruited to Rochester included a team with expertise in neural stem and precursor cells, which ultimately become brain cells. The team included Christoph Proschel, Ph.D.; Mark Noble, Ph.D., a co-discoverer of the first glial precursor cell known, which gives rise to cells known as oligodendrocytes; and Margot Mayer-Proschel, Ph.D., who discovered the earliest glial precursor known to date, which gives rise to both oligodendrocytes and cells known as astrocytes.
The group is among the best in the world at handling neural precursor cells, keeping them alive and manipulating the signals that the cells use to determine what type of brain cell to become. When Nathan lay ill, the team was available and ready to study his brain cells in unprecedented fashion.
Chris Proschel, research assistant professor in the Department of Biomedical Genetics, led the laboratory study of Nathan's cells. Since doctors know that the disease affects myelin, the fatty material that insulates nerves and allows them to send their signals crisply, Proschel's team expected to find defects in or a shortage of oligodendrocytes, the brain cells that produce myelin.
The team found no such thing. The oligodendrocytes looked normal and were present in healthy numbers – but the team did observe a dearth of astrocytes, and those that were present did not appear healthy. "Normally, astrocytes are much easier to grow than fragile neurons or oligodendrocytes," says Proschel. "So the last thing you'd expect is fewer astrocytes."