Niemann-Pick is a rare genetic
- Niemann-Pick disease is a rare genetic disorder
- It is also called "Children's Alzheimer's"
- FDA approved histone deacetylase inhibitors provided treatment in experimental mice
that is characterized by mental and physical degeneration of
children, noticeable by the time they reach adolescence. It
occurs in one in 150000 children and is also called "Children's Alzheimer's" though the disease has nothing in common
with the neurodegenerative disorder like Alzheimer's
Type C Disease
‘Histone deacetylase inhibitor delays neurodegeneration and increases the life span of mice with Niemann-Pick type C.’
autosomal genetic disease leads to the unusual accumulation of non-esterified
cholesterol in the lysosomal compartments of cells. This accumulation of
cholesterol occurs in the spleen, liver as well as the brain. The symptoms may
begin within a few months after birth or may even set in during adulthood.
- Ataxia (loss of control of bodily movements)
- Vertical gaze palsy ( The eyes cannot be moved up and down)
- Enlarged spleen
- Enlarged liver
Initially, only one or two symptoms arise during the start of the disease with
the progression of the disease leading to further complications. The disease is
always fatal and children with this type of
Niemann-Pick disease die by the time they reach their 20s.
When the disease
begins to show symptoms later in life, the progression is slower, but no individual with this type of disease has lived for longer
than 40 years of age.
associated with this disease, the trauma endured by parents of children
affected with Niemann-Pick type C disease and the problems faced by the
affected children encourage studies on a prospective cure for this disease.
Researchers Mohammed Suhail Alam and
colleagues studied the markers for Niemann-Pick type C disease in the plasma in
a quest to identify the disease early to slow the progression of the disease.
The article titled " Plasma Signature of
Neurological Disease in the Monogenetic Disorder Niemann-Pick Type C" was
published in The Journal of Chemical Biology
These researchers working on mice
found that the Purkinje cells present in the cerebellum were affected in
Niemann-Pick type C due to over-expression
of lysozyme leading to symptoms of ataxia
The affected mice, in this study,
were treated with hydroxypropyl-β-cyclodextrin (HPβCD) also called cyclodextrin.
- This was found to control the
inflammatory process in the liver but not in the brain.
- Moreover, it did not affect
transcripts of 24 hydroxylase which is specific to neurons, its product 24 hydroxycholesterol
is not a marker for the disease.
The researchers continued to study treatment
solutions for Niemann-Pick type C. Their work on the effect of histone deacetylase inhibitor
has raised hopes of a possible cure for the disease. The
article titled "Chronic administration of an HDAC inhibitor treats
both neurological and systemic Niemann-Pick type C disease in a mouse model"
published in the journal Science Translational Medicine
About the Study
Histone deacetylase inhibitors
(HDACi) are approved for the treatment of certain types of cancers.
The researchers used a triple
combination of -
- (HDACi) Vorinostat
- Hydroxypropyl β-cyclodextrin (which was found to be effective in
controlling inflammation in the liver of Niemann-Pick disease in their
- Polyethylene glycol (PEG)
The use of Vorinostat (HDACi) in
the treatment of Niemann-Pick Type C disease was studied previously by
researchers Paul Helquist and colleagues who found that Vorinostat increased
the level of NPC1 protein, which is found lacking in Niemann-Pick type C
patients. The researchers concluded that vorinostat is a promising drug but
that further study and clinical trials need to be carried out.
The current study by researchers Mohammed Suhail Alam and colleagues examined the effect of Vorinostat alone on mice with Niemann-Pick type C
disease as well as the effect of the triple combination. This helps in
identifying the most effective treatment measure.
Animals Under Study
The study was conducted on mouse
models with Niemann-Pick disease type C.
of Vorinostat (Histone deacetylase inhibitors (HDACi))
The administration of vorinostat alone ( single
agent administration) had an effect on Niemann-Pick Type C mouse cell lines, but it did not aid in increasing the period of survival of the
Administration of the Triple Combination
The administration of the triple
combination in low doses ( once a week) intra-peritoneally lead to:
- Preservation of Purkinje cells as
well as neuritis
- A delay in the neurodegenerative
- The increase in the lifespan of the
mouse by nearly 5 months
Niemann-Pick Type C disease patients is a difficult symptom to adjust to, as
most patients are young and have their whole life to lead. It is also very disturbing
for parents and other relatives to cope with the changes.
This study provides a ray of hope to such
patients and could possibly delay the symptoms and prolong their life.
Advancements in medical therapy like gene therapy
have also been utilized to
identify a cure for this disease.
3. Helquist P,
"Treatment of Niemann--pick
type C disease by histone deacetylase inhibitors.", Neurotherapeutics. 2013
4. Md. Suhail
Alam, Michelle Getz,
Safeukui, and Kasturi
Signature of Neurological Disease in the Monogenetic Disorder Niemann-Pick Type
C", J Biol Chem. 2014 Mar 21
5. Alam MS,
" Chronic administration of
an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C
disease in a mouse model.", Sci Transl Med. 2016 Feb