Scientific research can be a competitive enterprise, with researchers vying to win grants and keeping their findings secret, lest their articles get “scooped.” But this antagonistic approach is not the norm for a small cadre of scientists, including a key group at Penn’s School of Veterinary Medicine, who are focused on a rare disease called Niemann-Pick type C (NPC).
Their collegial attitude, openness in sharing experimental findings, and partnerships with families whom the disease has affected may result in the first effective treatment for NPC, prolonging the lives of children who would otherwise die before they leave their teen years.
NPC affects just one person in 150,000 and is sometimes referred to as “childhood Alzheimer’s” because of the progressive mental and physical decline seen in the children it afflicts. It’s a genetic condition that causes a malfunction in how cells process cholesterol in structures called lysosomes. Though researchers are still figuring out why, this results in a variety of disabling symptoms that come on slowly but inexorably.
“It’s a horrible disease,” says Charles Vite, an associate professor of veterinary neurology in Penn Vet’s Department of Clinical Studies. “Unlike a lot of other genetic diseases, there’s no hint that there’s anything wrong when the child is born. These are beautiful, normal kids until they reach school age. Then they start to have trouble with learning, they have difficulty in sports, some can’t talk well, some of them develop psychosis and seizures. Death usually occurs by 20.”
Yet a recent study led by Vite offers hope to affected children and their parents. Writing last month in Science Translational Medicine, Penn Vet researchers, together with colleagues from Janssen Research & Development, Washington University in St. Louis, the Albert Einstein College of Medicine, and France’s Institut National de la Santé et de la Recherche Médicale, reported that cats with the feline version of NPC that were treated with a compound called cyclodextrin showed vast improvements in their symptoms.
The study offered enough promise and reassurance that the treatment was safe for the FDA to approve the launch of a clinical trial in children, which began last year.
“Large animal models of human disease, like cats, are really helpful for determining what’s going to happen in a child when you’re treating them,” Vite says. “By using these natural models, the ultimate goal is to find something that helps your cat and your dog population and your human population, too.”
Starting in the early 2000s, various groups of researchers began realizing that cyclodextrin, which is a key ingredient in the odor-grabbing product Febreze, might be an effective way to ameliorate the effects of NPC, because it had been shown in cell culture to remove cholesterol from cells.
But when it was initially tested in mice, the results were disappointing, and it was set aside for a few years.
At that time, Vite and other researchers interested in NPC attended a meeting of the Ara Parseghian Medical Research Foundation. Parseghian is a former University of Notre Dame football coach who had three grandchildren die from NPC.
“At that meeting, we decided that it was worth looking at this drug a little bit more,” Vite says.
While his colleagues resumed testing the drug in mice and cell culture, Vite and his lab tested it in cats, which can naturally get the disease.
“The benefit of evaluating the therapy in cats was that they are large enough that we could repeatedly give cyclodextrin directly into the fluid around the brain as could be done in children,” Vite says.
NPC researchers from around the country—including Penn, the University of Texas Southwestern, Einstein, Washington University in St. Louis, the University of California San Francisco, the National Institutes of Health, Johnson & Johnson, and other centers—kept in close touch about the results. Mice receiving the treatment showed significant benefits. But Vite calls the results in cats “astonishing.”
Normally, untreated cats die by the time they are 6 months old. But cats that received infusions of cyclodextrin directly into the fluid surrounding their brain looked normal. Even at 18 months, they had only mild symptoms.
Today, some of these cats treated with the highest dose are more than 3 years old, and have gone on to have kittens.
Unfortunately, the treatment does cause hearing loss, though Vite and colleagues are searching for a compound that might have the same beneficial effects without this drawback.
To keep advancing this line of research, Vite and other NPC researchers spend more than an hour on the phone every other week, discussing preliminary results and new directions. And it’s not
just the close ties with other researchers that make the community unique—it’s the relationship with families of NPC patients. Vite has had children with NPC visit the cats in his lab, and corresponds regularly with parents of other patients. Private fundraising by parent groups contributes approximately 20 percent of his lab’s funding. Input from parents on how their children are doing when receiving cyclodextrin also helps when planning future studies in the cats.
“It makes it wonderful to come in every day to work on something you think is both appreciated and critically important to other people’s lives,” Vite says.