results of an early-stage clinical trial indicate that Cyclodextrin slows the
progression of Niemann-Pick type C, a neurological disease with serious
- 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
- Initial results appear promising, though further studies are
. 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 is being evaluated in clinical trials to slow the progression of Niemann-Pick C, a lysosomal storage disorder that causes neurological symptoms.
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.
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.
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:
patients were scored for the progression of the disease with the NPC
Neurological Severity Score
- 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 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
- 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.
- Niemann-Pick Disease Information Page - (https://www.ninds.nih.gov/Disorders/All-Disorders/Niemann-Pick-Disease-Information-Page)
- 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:http://dx.doi.org/10.1016/S0140-6736(17)31465-4