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.
8. 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
9. 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.
10. 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.
11. 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%
12. 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!
