Four years ago, Victoria Jackson, the creator of Victoria Jackson Cosmetics, was all about lip-gloss. Then, her middle child, Ali Guthy, started to lose her vision.
The diagnosis doctors provided was puzzling. The prognosis was worse. Her daughter had neuromyelitis optica (NMO) and she could be blind and paralyzed within four years.
From that moment, Jackson's life would never be the same. And neither would the lives of several researchers.
Jackson and her husband, Bill Guthy, quickly learned that almost no one studied this rare disease, which strikes fewer than one in 100,000 people. They traveled to Rochester, Minnesota, to see the nation's only expert, Dr. Brian Weinshenker, at the Mayo Clinic. But before they even left California, Jackson was beginning to plot.
"I was in action mode."
She told the surprised Mayo Clinic doctor, "I have a checkbook and I'm going to create a foundation and you and I are going to start our way in finding a cure."
Jackson quickly rallied experts in related areas and within weeks, researchers who did not know one another earlier were collaborating on the disease.
She has funded his work ever since through the Guthy-Jackson Charitable Foundation she and her husband created. "My focus went from mascara to medicine," she says. Ali, today an 18-year-old college freshman, is neither paralyzed nor blind.
"Stem cells would be an important piece of the potential therapeutics for NMO," Jackson says. "The work that CIRM is doing is really important."
In this disease that can lead to blindness and paralysis, a class of immune system antibodies run amok, attacking a protein called aquaporin 4 whenever they find it near the optic nerve and spinal cord.
Why the antibodies mistake self for invader is a mystery. Why they assault aquaporin 4 only near the optic nerve and spinal cord, and ignore it in the kidneys and elsewhere is also a puzzle. And it is a complete riddle how an attack on that protein leads to the destruction of myelin, the protective covering on nerves. When myelin degrades, nerves can no longer propagate signals.
For a long time, physicians managed NMO, also called Devic's disease, as if it was a variant of multiple sclerosis; both diseases wipe out myelin and, subsequently, nerve signaling. But the discovery of the antibody responsible for NMO less than a decade ago showed clinicians that NMO required a completely different approach.
Because NMO involves an immune system attack on self, steroids, with their ability to suppress immune response, provided the first valuable tool to arrest its advance. But treating NMO with steroids was like performing plastic surgery with a hammer. "A steroid doesn't care if it's killing a B cell, a T cell, a white cell or whatever," said Michael Yeaman, Ph.D., professor in the Division of Infectious Diseases at UCLA.
Steroid-treated patients were vulnerable to every virus and sniffle going around, and at an increasing risk of cancer with long-term use. Treatment options improved with the recent discovery that Rituximab, an antibody targeting B cells in B-cell lymphoma, also corralled the autoimmune destruction of NMO.
"Rituximab entered the NMO scene with a lot of promise, but it is only the beginning of the story," Yeaman said.
Better tools may be on the horizon. Phase 1 trials could begin in 2012 with an engineered antibody that acts as a burly bouncer to misguided antibodies. The antibody homes to the same aquaporin receptors the NMO antibodies favor and blocks them.
But stopping the advance of the disease solves only part of the NMO puzzle.
"Ultimately, reversing the damage caused by NMO or other autoimmune diseases will require regenerative medicines, and stem cells will play a key role in that respect," Yeaman says. "To restore the central nervous system, we're going to need regenerative help."