“This is,” said Charles H. Vite, DVM, PhD, “a rare and stunning story.” It is a story of creativity, collaboration and the promise of hope. For children and their families, a diagnosis of Niemann-Pick type C disease (NPC) is devastating. Recent results of a collaborative study involving Penn Vet offer real possibilities for treatment in multiple species suffering from this rare genetic disease.

What is it?

NPC starts with the accumulation of excessive amounts of cholesterol within the liver and brain. In people, where it affects primarily young children, there are only about 500 cases diagnosed worldwide. Early diagnosis is difficult, often initially mistaken for learning or intellectual disability or delayed development. It has been referred to as a childhood Alzheimer-like disease. Its results, however, are universally heartbreaking. A seemingly healthy child will experience progressive impairment of motor and intellectual function, and life expectancy is almost always under 20 years.

A collaborative effort

While there are no therapies currently approved by the U.S. Food and Drug Administration, a clinical trial with children began the last week in January to test cyclodextrin and evaluate it as a possible treatment for NPC. Research at Penn Vet paved the way for this encouraging study.

The goal of developing a safe and effective therapy, said associate professor Charles H. Vite, DVM, PhD, board-certified in Neurology, depended on strong corporate, intramural and national funding, of many labs to support the selection of potential compounds, animal studies, and bioanalytical and biomarker development.” Private support, frequently from parents with affected children, was also crucial.

That collaborative effort began seven years ago when Dr. Vite began to exchange information with Synthia Mellon, PhD (University of California San Francisco, School of Medicine), Steven U. Walkley, DVM, PhD (Albert Einstein College of Medicine, Bronx), and John Dietschy, MD (University of Texas Southwestern), who were testing the efficacy of a drug to treat NPC in mice. NPC is a naturally occurring disease in many species, including mice and cats, and when Dr. Vite took the next step in translating this drug for human use, he was using the feline model. The results were disappointing at first until the group discovered that it was actually cyclodextrin, a substance used to dissolve the original drug being investigated, which was the effective agent.

“It works wonderfully,” said Dr. Vite. Where cats with NPC would die at 24 weeks of age untreated, those treated with the drug are alive and well at over two years of age.

The National Institutes of Health (NIH) actively seeks collaborations to treat rare disorders. When it appeared as though cyclodextrin might be a drug that could progress towards clinical trials, the NIH, along with their National Center for Advancing Translational Sciences (NCATS), facilitated a collaboration to advance the research. They organized a team that included Dr. Vite; Dr. Walkley; Johnson & Johnson Pharmaceuticals; Daniel S. Ory, MD (Washington University, St Louis); Forbes Porter, MD (NIH); and others. (Dr. Porter’s daughter, coincidentally, is a third-year student at Penn Vet.) For three years, the team would meet by telephone at least twice a month.

Reaping the rewards

“The cat was the seminal part,” explained Dr. Vite, “because we administered the cyclodextrin into the nervous system, into the spinal fluid.” Based on what was learned about the pharmacokinetics and safety of cyclodextrin, it was determined that this would also be the best method for administering the drug to the children in the trials.

“It doesn’t get any better than finding something that treats animals, and then will go on to treat kids,” said Dr. Vite. “That’s the holy grail. That’s what keeps us going. And we are really excited about it.” The drug also has potential as a treatment for Alzheimer’s disease.

The clinical trial of cyclodextrin began on January 23 at the NIH Clinical Center. It couldn’t have happened without the input of academic researchers including Dr. Vite.