PROGERIA

“Still young yet looks old.”

Juvy M. Berdugo
Lea E. Magbanua
Hutchinson-Gilford Progeria Syndrome

PROGERIA
• Fact: “Progeria is
caused by a tiny point
mutation, a one letter
typo in the billions of
letter that make up
the chromosomal
book.”
(Progeria Research Foundation)
• is a rare genetic condition
that causes a child's body
to age fast.
• Most kids with Progeria do
not live past age 13. The
disease affects
• both sexes and all races
equally. It affects about 1
in every 4 million births
worldwide.
According to Progeria Research Foundation, there are 200 children around the
world who have progeria, with only (5) five reported cases in the Philippines.
Picure: 2006 Progeria Reunion in
Philadelphia

Zack between 7 and 9 months

Ana Rochelle Pondare, 18

Nova Mae O. Divinaflor, 8

Jeshaiah and Nezha Agbayani
WHAT CAUSES PROGERIA?

• Progeria is caused by a
mutation on the LMNA
gene. The mutation is
usually sporadic, and it is
during the cell division in a
newly conceived zygote or
in the gametes of one of
the parents.
Like described in the diagram above the mutation seen in this
disease is a point mutation at codon 608 in exon 11. It changes
cytosine to thymine. Therefore the splice site is activated in Exon 11.
This leads to the synthesis of abnormal Lamin A protein which is
known as Progerin.
Why is the LMNA gene so important ?
Where is the Lamina at?
Since there is a mutation…
This means the meshwork of proteins seen in the normal lamina cannot be
made, and instead a lamina without structure is produced.
Notice: the lamina is in a straight line
Normal Lamina: and all the proteins are organized.
Abnormal Nucleus (Nucleus of a someone with
Progeria)
• Notice: The lamina is not organized like in the normal nucleus of a cell. The
normal meshwork of proteins is not organized because progerin was made
and has its farnesyl group still attatched. This is then what causes nuclear
blebbling (meaning the cell does not have the normal round shape).

• **This abnormality in the nucleus is what scientist believe causes the

accelerated aging seen in children with Progeria. It is important to note that
this mutation does not happen in all of the cells of someone with Progeria,
but only in a percentage of them. In addition, it is also important to note that
although children with Progeria age in body at an accelerated pace, in mind
they accelerate at a normal pace. In mind they are as vibrant and full of
energy as any other child their age. This is because the LMNA is not
expressed by the brain cells; therefore the gene mutation does not affect the
brain.
CHARACTERISTICS & SIGNS

1) Growth failure
2 ) Loss of body fat and hair
3) Aged-looking skin
4) Stiffness of joints
5) Hip dislocation
6) Heart diseases
Since children with Progeria experience premature aging
they will experience diseases associated with aging like
high blood pressure, angina, enlarged heart, and/or heart
failure.
Heart disease is the number 1 reason children with
Progeria die. The average live expand of a child with
Progeria is anywhere from 8 to 21 years old but most die at
13.
TREATMENT AND RESEARCH

• Currently there is no cure for Progeria. Only the

symptoms can be treated. The Progeria Research
Foundation published a handbook for families and
doctors for suggestions on treatments. This handbook
was published in April 2010. Among the things this 100
page handbook discusses are the treatments that are
currently being studied.
• 3 drugs currently being studied in treatment trials for
Progeria:

• 1)Lonafarnib ( Farnesyltransferase Inhibitor (FTI) )

• 2) A statin called Pravastatin

• 3) A bisphosphonate called Zoledronic Acid

Lonafarnib

This drug is a farnesyltransferase inhibitor (FTI). FTI’s are a

class of drugs that inhibit an enzyme that is necessary to
attach to the farnesyl group to the progerin protein. If the
farnesyl group can not be attached, then the progerin
protein can not fully function because in order to damage
the cells and cause accelerated aging the progerin protein
needs to be farnesylated.
Pravastatin

This drug is commonly used to lower cholesterol and

prevent heart diseases. This drug is being used for children
with Progeria since it also has an effect on blocking the
production of the farnesyl molecule that is needed for
progerin to cause accelerated aging. This drug was
approved by the FDA in 2006 and according to them it
should be taken once a day.
Zoledronic Acid

It has also been used in children with a bone disease called

osteogenesis imperfecta, and for other bone problems.
Since a characteristic of children with Progeria is low bone
density it is believed that over time this drug will help
improve bone density. In addition, this drug has an effect on
blocking the production of the farnesyl molecule that is
needed for progerin to cause accelerated aging in children
with Progeria. The FDA approved it in 2001, and according
to them it should be administered intravenously several
times per year.
• Conclusion of the 3 drugs:
• All of the drugs discussed affect the progerin protein in
order to prevent it from affecting the cells of Progerian
patients. They all essentially affect the process in which
the cell makes the farnesyl group and attaches it to the
progerin protein.
• REMEMBER: If the farnesyl group is not attached to
the progerin protein than it will not be able to damage
the cell therefore because the cells are not damaged the
process of accelerated aging will not occur.
• Other drugs:

• low dose of Aspirin -prevent blood clots, prevent heart

attack and stroke
• Growth hormone -can help build height and weight.
• Physical and occupational therapy can help your child
keep moving if they have stiff joints or hip problems.
• Surgery. Some children may have coronary bypass
surgery or angioplasty to slow the progression of heart
disease.
• At home. They are more likely to get dehydrated, so they
need to drink plenty of water, especially when they're sick
or it's hot. Small meals more often can help them eat
enough, too. Cushioned shoes or inserts can ease
discomfort and encourage your child to play and stay
active.
 It's not the years in your
life that count.
It's the life in your years!
(by: Abe Lincoln)