What
is Pyrimethamine?
This
drug is approved for treating malaria, and has
also been found to have an effect on other
diseases such as toxoplasmosis, a
life-threatening parasitic infection. It has
also been used as an off-label therapy for
Tay-Sachs (Late Onset and Juvenile).
Pyrimethamine is based on pharmacological chaperone
technology.
In the
July issue of NTSAD's Research Review we
wrote:
In 2009,
NTSAD funded an investigator-sponsored clinical
trial at Hospital for Sick Children and NYU for
the treatment of Late Onset Tay-Sachs with
pyrimethamine (PYR) led by Drs. Joe Clarke and
Ed Kolodny. The results were published in
2011.
The
study concluded that leukocyte Hex A activity is
enhanced in vivo by treatment with PYR. However,
future studies were needed to assess protocol,
including dosage, and perform related
biochemical studies. An Israeli team of
researchers performed similar studies and
recently published their results. While they
also found that PYR increase Hex A activity in
LOTS patients, "the observed increase is
repeatedly transient and not associated with
discernible beneficial neurological or
psychiatric effects."
*
Click here to read the published
paper about
the
pyrimethamine studies conducted in
2011.
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What's
the Story with Daraprim?
This
drug (also known by its generic name,
pyrimethamine) has been in the news recently with the extreme
price increase from $13.50 a pill to $750 after
the pharmaceutical company producing it was
bought by another company. It has caught the
attention of the NY Attorney General and
presidential candidate Hillary
Clinton.
The
sudden increase in price will have a profound
effect on the treatment of patients suffering
from these illnesses, and for those who use
pyrimethamine for off-label use for
Late Onset or Juvenile Tay-Sachs.*
See the
sidebar for how patients
and patient groups like NTSAD can have a voice
when legislation is brought before the House and
Senate that can impact drug costs for orphan
drug therapies.
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What
is off-label use?
It
is when physicians treat their patients using
treatments approved for other uses but not
officially approved for use for their particular
disorder. The National Organization for Rare
Disorders (NORD) writes on their
website:
People
with rare diseases often have
difficulty
being
reimbursed for the care they receive because
that care is "off-label" and may not be covered
by health insurance. This financial burden can
be an enormous strain on patients and families,
especially when the cost of off-label treatments
runs very high.
Another
drug that has an off-label use is miglustat
(also known as Zavesca) which is a potential
substrate reduction therapy for the lysosomal
storage disorders. Read the
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What is a
Pharmacological Chaperone?
Pharmacological chaperone
technology involves the use of small
molecules that selectively bind to and stabilize
proteins in cells, leading to improved protein
folding and trafficking, and increased activity.
In lysosomal storage disorders, the target
protein is an enzyme that works in the lysosome to break down
substrate. Due to genetic mutations,
lysosomal enzymes may be misfolded and unstable,
which may hamper the protein's ability to be
trafficked through the cell.
In
lysosomal storage disorders, the binding of the
pharmacological chaperone to the active site of
the misfolded protein in the endoplasmic reticulum (ER) of
the cell helps the protein fold into its correct
three-dimensional shape. Stabilization of the
protein allows the protein-chaperone complex to
pass through the quality control system of the
ER. The protein-chaperone complex is then
properly trafficked from the ER, through the
Golgi apparatus, to the lysosome, which is the
protein's final destination. Once in the
lysosome, the pharmacological chaperone is
displaced from the active site of the
protein. This allows the protein, which is
biologically active, to break down the natural
substrate in the
lysosome."
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What Questions Do You Have about
Research?
We want to hear from you and
address any topics or answer any questions you
may have about research. Our Research Initiative
Committee is a group of knowledgeable friends
who are ready to tackle the tough questions and
address the topics that are meaningful to you.
Send Diana an email here with your
ideas for next month's issue for November 13,
2015. | | |
21st
Century Act Passes
The
21st Century Cures Act passed in the House this
past summer. An important part of the act
addresses affordable accessibility to potential
treatments. Drugs like Daraprim that have an
off-label use should be more affordable as
sometimes these are an individual's only option
for any kind of treatment.
The
Act passed thanks to the people whose shouts and
letters made a difference. The efforts of
NTSAD's advocacy partners - NORD, the EveryLife
Foundation and the Rare Disease Legislative
Advocates - keep us posted on rare disease
legislation that can have a profound impact on
all of us as treatments are researched and
hopefully brought to market.
Now,
NTSAD has been asked to get involved in the
advocacy for the Senate phase called the Innovation for Healthier
Americans. Stay tuned for future
announcements about how you can play a role in
getting the Act
approved! |
2015 Day of Hope
The Fifth Annual Day of Hope is
still going strong. To date over $27,000 has
been raised in the last month!There are still a
few events happening in the coming
weeks.
It's never too late to give to
research.
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Late Onset
Natural History Studies
National
Institutes of Health (NIH)
National
Human Genome Research Institute
Bethesda,
Maryland
GM1
or GM2 gangliosidosis
(Infantile,
Juvenile, Late Onset)
Mass
General Hospital (MGH)
Boston,
Massachusetts
Late
Onset Tay-Sachs, Late Onset Sandhoff or Late
Onset GM1
University
of Minnesota (UMN)
Clinical
and Translational
Science
Institute
Minneapolis,
Minnesota
Infantile/Juvenile/Late
Onset Tay-Sachs or Sandhoff
diseases
For
more information about these studies, contact
Diana, Director of Family Services, here. |
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you on Facebook and
Twitter?
patient advocacy, and
more. | |
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