Download Gene Therapy for Choroideremia

Gene Therapy for
Choroideremia
by: Jennifer Chick, Barbara Gonzalez, Kenneth Karaivanov, Christine Murphy, Sean Roche,
Michele Rozier, and Gabriel Stapleton
What is Gene Therapy?
•Uses DNA as a drug to treat disease
•Uses functional DNA to replace mutated gene
•Three approaches to gene therapy
•1,700 clinical trials
•Major successes started in 2006
•2012 was first approved clinical trial
Timeline of Gene Therapy
A paper was
proposed that
claimed “good
DNA” could
replace defective
DNA
1990
1972
First Gene
Therapy case by
William
Anderson on a
girl with an
immune
deficiency
1992
First major
setback in
gene therapy
when Jesse
Gelsinger
died in a
2003
clinical trial
First stem cell
1999
procedure
using
hematopoietic
cells to correct
a hereditary
disease
Successfully
treated aspects
Melanoma,
granulomatous
disease, and
HIV
2007
2006
Gene therapy
is used to
access the
brain with
liposomes
6 patients
suffering from
Choroideremia,
all vision was
improved after
treatment.
First gene 2014
therapy for
inherited
retinal
disease
Now
Most recently
there have
been
promising
results with
treatment of
HIV patients
iClicker: Would you feel comfortable
receiving gene therapy as treatment
for an inherited disease or disorder?
A. Yes
B. No
C. Unsure
iClicker: Which of these diseases does not
have the potential to be treated with gene
therapy?
A. Common Cold
B. Parkinson’s Disease
C. Cancer
D. HIV/AIDS
E. Hemophilia
Vectors and Gene Therapy
Parts of the vector
● Promoter
● Enhancer
● Functional copy of the gene
Possible Issues with Gene Therapy
● Immune rejection of foreign vectors could be
dangerous.
● Researching and synthesizing vectors that
work is very expensive.
● Vectors integrate into the DNA. Possible
gene disruption?
● Very individualized response to complex
diseases
Structure & Function of Human Eye
●
●
●
●
Cornea:
○
Referred to as the “window of the eye”
○
It is composed of 5 layers
■
Outermost layer is the epithelium which provides protection
■
Inner layers provide strength
Pupil:
○
Black circle in the middle of the eye
○
Controls the amount of light entering the eye
■
The pupil becomes smaller to allow less light through in a bright environment
■
The pupil expands to allow more light to reach the back of the eye in a dark
environment.
Iris:
○
The colored part of the eye surrounding the pupil.
○
Controls size of the pupil
Sclera:
Structure & Function of Human Eye
●
●
Aqueous Humor:
○
Thin, watery fluid that fills the space between the cornea and the iris.
○
Nourishes the cornea and the lens.
○
Gives the eye its shape.
Lens:
○
The clear structure located behind the pupil.
○
Provides fine-tuning for focusing and reading.
■
●
●
Performs this function by altering its shape
Vitreous Humor:
○
The clear, gel-like substance located inside the eye’s cavity.
○
Provides a spherical shape to the eye.
Retina:
○
Consists of fine nerve tissue which lines the inside wall of the eye and acts like
a film in a camera
Structure & Function of Human Eye
●
The eye is systematically separate
from the rest of the body.
●
Light enters the eye through the
cornea via the pupil at the center of
the iris.
●
The pupil controls the amount of light
admitted while the cornea does most
of the focusing.
●
Light then passes through the lens,
where it is finely focused, and then
travels back through the eye to the
retina.
●
The retina interprets images and
then sends the information to the
brain via the optic nerve.
•
•
What is Choroideremia?
Choroideremia is a disease of the eye associated with progressive vision
loss
It accounts for roughly 4% of blindness related disorders.
o
It mainly affects males, but women who hold one copy of the gene (carriers), may develop
eye impairment later on in life, as well.
o
Inherited via an X-linked recessive pattern.

Gene responsible for Choroideremia, CHM, found on the X chromosome.
Why Mainly Males Are Affected
•
Inherited via an X-linked recessive pattern.
o It is much more common for males to be affected by X-linked
recessive conditions, such as Choroideremia
 CHM located on the X chromosome.
o Since males only have one copy of the X chromosome, one altered
copy of the gene is sufficient to cause condition
o For females to have the condition, both of their X chromosomes need
to have the same mutation
o Affected males can pass the link on to their female offspring, but not to
their male. A carrier female has 50% chance of passing on to
offspring.
Symptoms of Choroideremia
o It is estimated that 1/50,000 people are affected by Choroideremia,
although, scientists believe that its prevalence may actually be more
substantial.
 This is because Choroideremia shares many similarities to other eye
disorders and therefore may be misdiagnosed.
o First symptom is usually impairment of night vision (“night blindness”)
 can occur in early childhood
o The disease develops further to affect the field of vision
 Field of vision progressively narrows (“tunnel vision”)
o Loss of ability to see detail follows (“visual acuity”)
o For all individuals, the disease gets worse over time, but the rate of
progression varies among individuals
 All affected individuals eventually go completely blind by late
•
How is the Eye Affected by
Choroideremia?
The eye experiences an ongoing loss of cells (atrophy)
in the retina and its network of blood vessels
o
This network of blood vessels is known as the
choroid
o
Eventually the light detecting cells in the retina die
completely, resulting in blindness
How Gene Therapy is Used in Treating Choroideremia
•
This specific gene therapy
involves inserting a gene into the
eye to repair light detecting cells
o This treatment not only
prevents further degeneration
but also improves eyesight
o This is the first gene therapy
procedure to target
photoreceptors in the eye
Diagram of Choroideremia Gene Therapy
Significance of Choroideremia treatment for
other similar retinal diseases
•
•
Successful use of gene therapy for choroideremia offers hope for
treatment of other retinal diseases
o There are currently other successful trials using gene therapy
to treat retinal diseases
o Knowledge gained from choroideremia trials is very useful
 Offers hope for the human trials being conducted for other
diseases such as age related macular degeneration,
glaucoma and Usher Syndrome
Still some uncertainty about long term cure
o Not sure if gene therapy will slow retinal degeneration in the
long term
From Choroideremia: Applying Gene
Therapy to treat other retinal diseases
● 1) MACULAR DEGENERATION
Macular degeneration, or age-related macular
degeneration (AMD), is a leading cause of vision loss in
Americans 60 and older. It is a disease that destroys
your sharp, central vision. You need central vision to see
objects clearly and to do tasks such as reading and
driving.
Gene Therapy & Macular degeneration
● Just as with the process involved in treating Choroideremia, other eyesight conditions such as wet-related macular degeneration can also be
treated using genes therapy.
● This is done through a virus vector (a sort of transport vehicle) carries the
therapy to the retina. A piece of DNA is spliced into an engineered
virus.This will code for a vascular endothelial growth factor (VEGF)binding protein that is inserted in the eye through subretinal
injections.The epithelial architecture of the retina allows the vector to
come into contact with the populations of cells and the contact with
the systemic immune system promotes tolerance of foreign antigens.
Gene Therapy & Other Retinal diseases
iClicker: After learning the information from
this presentation, would you feel comfortable
receiving gene therapy as treatment for an
inherited disease or disorder?
A. Yes
B. No
C. Unsure
iClicker: Should people be allowed to use
gene therapy to enhance basic human
traits, like height, skin color, or behavioral
characteristics?
A. Yes
B. No
C. Unsure