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

Douvlataniotis Karolos

DNADeoxyribonucleic 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

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

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. Besides inherited dieseases, it can be used against cancer and even

infectious diseases.

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.

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.

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.

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

Gene Therapy and Parkinson'sParkinson'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.

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.

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%

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!

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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.shtml#whatis

http://www.msnbc.msn.com/id/19355047/ns/health-health_care/t/gene-therapy-offers-hope-easing-parkinsons/#.T5XPaNUtA8p

http://www.medicalnewstoday.com/articles/238992.php

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http://www.medicalnewstoday.com/articles/219638.php