New results raise hopes of a treatment for Niemann-Pick type C1

By Paul Basilio, MDLinx
Published August 14, 2017

Key Takeaways

New findings published in The Lancet show that an experimental drug may slow the progression of the fatal neurologic disease Niemann-Pick type C1 (NPC1). The study was led by researchers at the National Institutes of Health (NIH).

NPC1 is a rare genetic disorder that causes a progressively severe decline in neurologic and cognitive functions. It primarily affects children and adolescents. Currently, there are no FDA-approved treatments for the condition.

The experimental drug is called 2-hydroxypropyl-beta-cyclodextrin (VTS-270). It is being tested under a cooperative research and development agreement (CRADA) between NIH and Sucampo Pharmaceuticals, Inc. In April 2017, Sucampo acquired Vtesse Inc., which previously had been developing VTS-270.

The phase 1/2a clinical trial was designed to test the drug’s safety and effectiveness. Fourteen participants ranging from ages 4 to 23 years of age received the experimental drug once monthly at the NIH for 12 to 18 months. Another group of three participants received the drug every two weeks for 18 months at Rush University Medical Center in Chicago.

Participants were initially divided into groups that received different doses of the drug. However, after observing that the drug was safe and well-tolerated by those receiving the highest doses, the researchers increased dosing for all participants. Their progress was compared to a previous group of 21 NPC1 participants enrolled in an earlier study that documented disease progression. 

“The results are very encouraging and support continued development of VTS-270 for treating NPC1,” said Forbes D. Porter, MD, PhD, senior author and Clinical Director of the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Compared to untreated patients we followed in an earlier study, participants who received VTS-270 scored better on a scale used to evaluate disease severity and progression, including elements such as speech, cognition and mobility.”

No serious adverse outcomes were found to be related to the drug. Most participants had hearing loss due to the disease prior to the study, and there were reports of additional hearing loss after treatment. This corroborates earlier studies had shown that the treatment carries the risk for hearing loss. In the current study, hearing loss was compensated with hearing aids.

NPC1 symptoms result from cholesterol buildup in brain cells, so the researchers also measured cholesterol metabolism in the participants’ central nervous system. The researchers found that a molecule derived from cholesterol metabolism in neurons—24(S)-hydroxycholesterol—had increased after treatment.

In addition, most participants had lower levels of two proteins indicative of brain injury, FABP3 and calbindin D. Study authors say the results suggest that VTS-270 can improve cholesterol metabolism in neurons, thereby targeting the root of the problem.

A neurological severity score was also used to evaluate the drug’s effectiveness. Higher scores indicate more severe effects from the disease. VTS-270-treated participants had lower scores in measures of cognition and speech, with mobility scores also trending lower when compared to an earlier group of patients who had not received the drug. The authors believe these differences indicate that treatment with the drug can stabilize or slow disease progression.

For more information about the study, click here.

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