Project to coursera Neurobiology course

1. Gene Therapy & Neurobiology
An application to Parkinson's Disease.
Douvlataniotis Karolos

2. DNA
Deoxyribonucleic acid (DNA) is a molecule which encodes and controls all
te genetic information which defy the biological growth of every organism.
It has the shape of a double helix and is strucutred by many nucleoids,
which are made by 2 of the 4 nucleobases, deoxyribose and a phosphate
group

3. Genes
Genes are a specific sequence of bases, in a specific
part of the DNA, which defy the synthesis of a
protein.

4. What's gene therapy?
Some people may have one or more defective genes,
which could lead to a certain disease, the so called
inherited diseases.
● Gene therapy is a technique that allows us to repair
those problematic genes.

5. History of gene therapy
● Gene therapy is based on the work of many scientists over
the last century and even further. As for it's practical
applications, the key point was at 2000, when 10 people
with Severe combined immunodeficiency went through
gene therapy with very promising results.

6. How does gene therapy work;
Usually, a normal gene is inserted in the genome to
replace a faulty one. The insertion can be done via
various ways:
● Physical methods such as electroporation
● Chemical methods (e.g Lipoplexes, Inorganic
Nanoparticles )
● Injections of Naked DNA
● Viral Transfer, which is the most common and
successful method.

7. Viral Vectors
The viruses used in gene therapy are usually Adenoviridae and
Retroviridae, both having different pros and cons.
● Gene therapy utilizes the viral replication; basically the virus
enters a cell (host) and latches it's genome onto the host's
DNA, duplicating itself every time the host cell divides.

10. Problems with Gene therapy
● Short Term results. Patients must undergo treatment
every few months or years.
● Immunological response, since our body can identify
and destroy the used viral vector.
● The cons of the viral vectors, e.g a virus may mutate
and become pathogenic
● Some diseases are multi-gene, meaning we need to
repair more than one faulty gene.
● As with every treatment, issues of ethics may arise

11. Gene Therapy and Parkinson's
Parkinson's Disease (PD) is a degenerative disorder of the central
nervous system. It's symptoms are mainly movement related and
consist of shaking, rigidity, slowness of movement and difficulty
with walking and gait. Even awereness, thinking and memory issues
may arise in more advanced stages.
●Currently there is no cure, but medi-
cation is used to treat the symptoms.

12. Gene Therapy and Parkinson's
●The motor symptoms of Parkinson's disease result from
the death of dopamine-generating cells in the substantia
nigra.
●The substantia nigra is a brain structure located in the
mesencephalon (midbrain) that plays an important role in
reward, addiction, and movement.
●The cause of the cellular death is unkown.
●Loss of dopamine causes nerve cells to fire abnormally
and excessively, which disrupts the functioning of other
portions of the motor system that are directly responsible
for movement, causing excess neuronal activity in some
areas and diminished activity in others.

13. GAD Treatment
One experimental gene therapy is the GAD treatment. A viral
vector delivers a gene that increases the neurotransmiter GABA,
which helps to quite down the symptoms. There were 2 trials, on
2007 and 2011 with the following characteristics :
● Phase 1 of the trial
● 12 patients participated
● Treatment took place on the one
side of the brain
● There were no side effects
● One year later there was a motor
improvement by 25%
● Phase II of the trial
● Double-Blind trial
● 45 people participated (22
patients)
● Common side effects were
nausia and headaches
● 6 months later there was
improvement by 21,3%

15. What i learned from the Course
As an undergrad biomedical scientist, with an interest in
molecular neurobilogy, i was able understand a bit more
about how the brain works; identify better the structures of
the brain, the physiology of the neurons in general, as well
as the pathological base from the various disorders of the
neurvous system.
Thans to professor Mason for the constant motivation and
the coursera team for helping to bring all this together!

16. References
Immunology Goldsby R.,Kindt T.,Osborne B.,Kuby J. : 696
ΘΕΟΧ. ΑΛ ΠΑΤΑΡΓΙΑΣ & ΒΑΣ. Γ. ΑΛΕΠΟΡΟΥ. ΓΕΝΕΤΙΚΗ
ΑΝΘΡΩΠΟΥ Β' ΕΚΔΟΣΗ 2005: 397:400-402.
Πλαγεράς Π, Γεροβασίλη Α, Παπαϊωάννου Α, Εφαρμογές Μοριακής
Διαγνωστικής 2011: 65
http://en.wikipedia.org/wiki/Gene_therapy#cite_note-18
http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.
http://www.msnbc.msn.com/id/19355047/ns/health-health_care/t/gene-therapy-
http://www.medicalnewstoday.com/articles/238992.php
http://www.nytimes.com/2011/12/11/health/research/hemophilia-b-gene-therap
http://www.medicalnewstoday.com/articles/219638.php