Cyclodextrin slows progression of Niemann–Pick type C.
The study, led by researchers at Washington University School of Medicine in St. Louis and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH), was published Aug. 10 in The Lancet journal.

“We were surprised to see evidence that this therapy could slow progression of the disease and, in some cases, get back some function – speech in particular,” said first author Daniel S. Ory, MD, the Alan A. and Edith L. Wolff Professor of Cardiology at Washington University School of Medicine in St. Louis. “In a neurodegenerative disease, therapies can’t recover neurons that have died. But if some brain cells are dysfunctional rather than dead, it seems this drug can recover some of that function.”

In the combined phase one/two clinical trial, 14 NPC patients who were ages 4 to 23 years and showing neurological symptoms were given cyclodextrin, administered into the spinal column once per month for 12 to 18 months. Another three patients were given cyclodextrin in the spinal column every two weeks for 18 months. Since cyclodextrin does not cross into the brain from the bloodstream, the drug must be injected into the spinal column by lumbar puncture, an outpatient procedure often referred to as a spinal tap. The study did not have a control group that received a placebo, so researchers compared the patients’ progression with historical data collected from past NPC patients. Doctors used a specialized scoring system to measure disease progression. Called the NPC Neurological Severity Score, it helps assess eye movement, gait, speech, swallowing, fine motor skills, cognition, hearing, memory, and presence and severity of seizures.

The historical data from past NPC patients showed that patients’ scores increased – meaning the disease worsened – an average of 2.9 points per year. In contrast, the scores of patients in the trial increased an average of 1.2 points per year, a difference that is statistically significant. The improvements compared with the historical data were seen most in gait, cognition and speech.

Seven of the 14 patients saw one–point improvements in their own scores in one or two categories compared with their own baseline scores in those categories over the course of the trial. The remaining seven either remained unchanged or experienced worsening scores. Though, on average, their scores worsened less than patients in the historical comparison group.

However, hearing loss, a symptom of NPC, was also a major adverse effect of the drug.

“A therapy that causes hearing loss is not ideal. But since the disease itself causes hearing loss, we felt that this side effect may be a reasonable trade–off, given the alternative decline and death that the disease also causes,” Ory said.

Ory added that the patients were able to use hearing aids to maintain quality of life.

Cyclodextrin appears to release the trapped cholesterol, allowing it to be metabolized and removed from the cell. A different drug called miglustat also shows evidence of slowing NPC progression. Though miglustat is approved for treating NPC in Europe, Canada and a few other countries, the FDA – citing a need for more data – has declined to approve it for treating NPC in the United States.

In addition to demonstrating that disease progression slowed with cyclodextrin, Ory and his colleagues assessed biomarker measurements in the blood that showed evidence that the drug was removing cholesterol from the brain. Such biomarkers raise the possibility of early diagnosis, since levels of certain compounds differ between healthy people and patients with NPC, even before the onset of symptoms.