Illustration by Scotty Reifsnyder
Chris Hobler was a handsome, 35-year-old husband and father living in Milton Mills, N.H. A graduate of John Burroughs School, he fronted the band Sonic Joyride, something of an indie sensation during the ’90s. One day in 2001, Hobler noticed he was slurring his words. Soon after, he was diagnosed with amyotrophic lateral sclerosis, or ALS, the same disease that in 1961 took the life of his grandfather, James A. Maritz Sr., founder of Maritz Inc.
Hoping to learn more about the causes of ALS, Hobler soon discovered that scientists had made little progress in understanding the disease since his grandfather was afflicted with it four decades earlier. The problem, he recognized, was that the relatively small population of those with what are termed “orphan diseases” offered limited profitability for pharmaceutical companies, since each of the more than 7,000 such disorders affects fewer than 200,000 Americans at any one time. Moreover, many of the scientists investigating those diseases weren’t sharing relevant information with each other.
So in 2002, three years before his death, Hobler started ALS Hope, a nonprofit devoted to the idea that collaborative research could lead to discoveries. The nonprofit later widened its focus to other neurological disorders, including strokes, cerebral palsy, Alzheimer’s disease,
multiple sclerosis, Parkinson’s disease, epilepsy, and traumatic spinal-cord and brain injury. In fall 2004, it was renamed Hope Happens.
Today, Hobler’s dream lives on at the Hope Center for Neurological Disorders. The consortium consists of 80 physician-scientists and a total workforce of 400 at Washington University and its School of Medicine. The 80 labs involved each have a director and team of graduate students, postgraduate fellows, and technicians from a wide variety of disciplines: genetics, biology, biophysics, mechanical engineering, neurology, neuroscience, radiology, pathology. All of them, Hope Center executive director Anneliese Schaefer explains, “are focused on the mechanism of the diseases.” What the teams learn is shared with others, in pursuit of discovering cures for neurological diseases across the board.
So how exactly does such an ambitious initiative find funding?
That’s where Hope Happens comes in.
“Our function in life is fundraising for the Hope Center,” explains Bob Kindle, executive director of Hope Happens. In 2008, the Danforth Foundation awarded the center a $10 million grant that Wash. U. and Hope Happens aim to match by December 2013. The funds raised support the labs and provide top-of-the-line equipment and expertise.
“What the Hope Center does is create a pool for resources,” says Dr. Marc Diamond, associate professor of neurology. “No individual lab can afford to buy a $250,000 or $500,000 microscope unless they are an incredibly well-funded lab, of which there are just a few in the country. And you have to hire a technician; it would make absolutely no sense for any individual lab in the community to do that.” The center funds pilot projects, which must involve two or more labs; only three or four of the projects are funded annually, and each gets $100,000 to use over the course of two years.
The effort is attracting scientists from across the country. “I was really drawn to this institution because it is so collaborative, and in particular, there is a focus on neurodegenerative diseases,” says Diamond, who joined the Hope Center a year ago from an associate professorship at the University of California, San Francisco. “Wash. U. is very unusual—among the top five med schools in the country, it is probably the only one that is so collaborative and supportive of the faculty.”
The entire process is a team effort. Diamond’s lab, for example, is currently collaborating on projects with six other labs. One of the primary focuses of the studies is protein aggregation, a process where proteins start to misfold and clump in nerve cells. “They interfere with nerve-cell function, and they cause nerve cells to die,” says Schaefer.
Alison Goate, the Hope Center’s director, has focused her research on Alzheimer’s patients. As with everyone else at the center, the accomplished geneticist shares her findings with other scientists, hoping to discover more about the underlying causes of neurodegenerative diseases. “Some forms of these diseases are inherited and caused by a mutation or a change in the DNA in a single gene,” says Goate. “In the families, there is a genetic change which will predispose you to aggregate these proteins.”
The process usually doesn’t start until middle age, though (“You don’t meet a 5-year-old with Alzheimer’s,” says Goate), which leads to another set of questions: Why then? What sets the process in motion? How does it turn so virulent so quickly?
“Why don’t you just have one group of cells go bad?” Diamond asks. “Why does it have to go everywhere? The idea that we have been testing and what we think is true is that when a protein goes through this aggregation process in a single cell, the aggregates that form are released outside the cell, and they enter neighboring cells. Now a neighboring cell has a protein aggregate and can amplify its aggregation. And so on and so on and so on.
“It is sort of like falling dominoes,” he continues. “This is a new way to think of neurodegenerative diseases—it is not just a single cell going bad, but the actual connections between the cells facilitate the spread of the disease through the brain.”
To test that hypothesis, scientists are injecting infected cells into mice and breeding them, so the disease—be it Huntington’s, Parkinson’s, or ALS—shows up in second and third generations. Dr. David Holtzman, chairman of Wash. U.’s Department of Neurology, has implanted catheters into some of the infected mice’s brains to measure the levels of proteins floating between the cells. “If you could keep [the proteins] from moving, you could keep the disease from advancing,” says Diamond, growing more animated by the minute.
Holtzman’s approach is just one of many taken at the Hope Center.
Dr. David Brody, who organizes the center’s Neurotrauma Research Interest Group, works with soldiers who have fought in Iraq and Afghanistan, as well as retired NFL football players. He’s found that those who’ve sustained traumatic brain injuries tend to be at higher risk, long-term, of developing Alzheimer’s.
Dr. Timothy Miller, director of the Christopher Wells Hobler Laboratory for ALS Research, has a new ALS treatment going into a Phase I clinical trial. It aims to inhibit the formation of SOD1, the mutant protein that’s associated with an estimated 20 percent of familial cases of ALS. “The idea is that if you have a bad gene and you can do intervention to make less of that gene, you will make the person better,” says Diamond, who works in a lab next to Miller’s. “It has been shown in animals that that works.” The first clinical trial will determine whether it is safe to inject the new antisense drug, which works to stop a particular gene from creating the SOD1 protein, into a patient’s spinal column.
For physicians, researchers, and patients, such research does exactly what the center’s name implies, and what Hobler envisioned: It creates hope.
“I wouldn’t be here if there wasn’t cause to be optimistic,” says Schaefer. “We won’t have a cure tomorrow, but in our lifetimes, we will have steps in place to have a cure in the future.”
