Health In Focus
  • Patients with Niemann-Pick disorder have very limited treatment options. Miglustat is the only drug that is currently approved for its treatment in Europe
  • Scientists are evaluating the use of Cyclodextrin in these patients
  • Initial results appear promising, though further studies are required

The results of an early-stage clinical trial indicate that Cyclodextrin slows the progression of Niemann-Pick type C, a neurological disease with serious consequences. The study was published in The Lancet.

Niemann-pick type C (NPC) is a rare neurological disorder where harmful levels of lipids (fats) accumulate in the body. Type A is the most serious form of the disorder, with infants succumbing to it by the age of 18 months. Type B usually appears in the preteen years, while type C can appear either early in life, or later during teenage or in adulthood. Type C can cause extensive brain damage, though the liver and spleen are also affected. The affected person may succumb to the disease in infancy if it is severe, or may go on to live into adulthood in less severe cases, though most individuals succumb to it by the age of 20 years.
Cyclodextrin Shows Promise in Niemann-Pick Type C Disease

Treatment options are very limited for Niemann-Pick disorder. Miglustat is available for treatment in Europe and Canada, but is not yet approved by the US Food and Drug Administration (FDA). Thus, any research in the field can provide hope for the patients.

Animal studies in cat and mouse models of Niemann-Pick disorder have indicated the possible benefit of Cyclodextrin. It delayed neuronal cell loss in the cerebellum, slowed the progression of neurological manifestations, and increased the lifespan. Based on the positive findings, Cyclodextrin was tested in a small clinical trial in patients affected with the disorder.

In their study, the researchers used cyclodextrin 2-hydroxypropyl-beta-cyclodextrin (HPβCD) to treat fourteen patients with Niemann-Pick Disease type C. These individuals were between the ages of 4 and 23 years and showed neurological symptoms. Cyclodextrin has been previously used to dissolve medications in water.

The medication (HPβCD) was injected into the spinal column in the lower back once a month for 12 to 18 months. Three additional patients were administered the medication every 2 weeks for 18 months. At the end of the study, the scientists found that:
  • The level of 24(S)-hydroxycholesterol, which is a product of cholesterol metabolism in the neurons, increased in the blood and the cerebrospinal fluid following treatment. This indicates that the lipids were being metabolized. It has been suggested that cyclodextrin improves cholesterol metabolism by releasing cholesterol trapped within small cellular organelles called lysosomes, so that they can be metabolized and eliminated by the body.
  • The levels of the two proteins FABP3 and calbindin D in the cerebrospinal fluid, which indicate brain injury was reduced. This indicated a reduction in brain damage following the treatment.
The patients were scored for the progression of the disease with the NPC Neurological Severity Score. The score rates functions like eye movement, gait, speech, swallowing, fine motor skills, cognition, hearing, memory, and presence and severity of seizures on a scale of 0 to 5, with 5 being severe disability or loss of function. The scientists conclude that:
  • The score increased at an average of 1.2 points per year. This was in contrast to what was noted in a previous study on 21 patients in which the patients experienced an increase in 2.9 points per year. Since the worsening of the scores was less than that compared to the earlier study, it suggests that the treatment slowed the progression of the disorder.
  • HPβCD helped to get back some functions like speech in some cases. The improvement was also noted with gait and cognition. Thus, cyclodextrin may help to restore the function of some dysfunctional neurons.
  • It however accelerated hearing loss, which is also a symptom of Niemann Pick C. The patients were able to maintain their quality of life with the use of hearing aids.
A disadvantage of the medication is that, since it does not cross into the brain when given as an injection into the vein, it has to be injected into the spinal column.

If positive results are obtained from further studies, it is likely that the drug could be approved and will provide a treatment option for patients with Niemann-Pick disease.

Reference :
  1. Niemann-Pick Disease Information Page - (
  2. Ory DS, et al. Intrathecal 2-hydroxypropyl-beta-cyclodextrin decreases neurological disease progression in Niemann-Pick Disease, type C1: an ad-hoc analysis of a non-randomized, open-label, phase 1/2 trial. The Lancet (2017) DOI:
Source: Medindia

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