Gene Therapy for Parkinson's Disease

Parkinson's disease (PD) is decribed as loss of dopaminergic neurons that located at the substantia nigra. PD causes changes in balancing both expiratory and inbitory pathways of brain system thus affecting movement control by the brain.

By medication approaches in mainstream therapy is that taking dopamine repalacement is commonly used. Other than that, surgical treatment to improve motor function and increasing brain's cell activities also have been done to cure PD or reduce PD's symptoms (Deep brain stimulation).

For medication ( taking drugs) approach, patients should be respond well for number of years. But, for a long term treatment, " wearing off" could possibly happened as it will develop after years of treatment with levadopa (dopamine replacement)

Gene Therapy (GT)

GT approach have potential advantages that could be useful in treating PD. By concept, GT approach will make the cell to produce protein that they do not normally produce which genes was inserted and provide specific genetic order or instructions for cell to produce desired protein thus enhance the possibility of curing PD. The protein produced are formed in normal cellular division and proliferation and give benefit of less causing side-effects.

More than that, GT could target specifically to it's target location where the treatment are needed. GT also does need or relying on any mechanical or electrical method which make it is the best way to curing PD and produce less side-effects.

The treatment strategy

Treatment strategies combination are needed which protein and target location of the treatment should be identified. For a simple example :

1. A strategy to improve the delivery dopamine to the region of the brain of PD's patients
2. In the other hand, one more strategy was done at the same time to provide growth factor support to brain regions that could help recover damaged nerve cell and eventually will reduce PD's progressions.

GT relies on transporting DNA into targeted brain's cell. A vector was needed as to protect and transport the DNA so that it can be delivered at exact location of target site. For this case, most common vectors are used which are adeno-associated virus type 2 , adenovirus, lentivirus and herpes virus. The selected virus was used as these type of virus does not have any ability to reproduce themselves and did not causing disease.

Adeno-associated virus type 2 (AAV-2) is one imprortant type of virus which it carries DNA only to neurons and once inside the brain, it was proven to efficiently carry DNA to neuron that affected in PD. Most GT studies shows that they will use AAV-2 as vector

Once vector have selected, the treatment should be administered on relevant area of brain (Basal Ganglia).

Basal Ganglia are part of interconnected deep brain area that involves in control for movement. The pathways of Basal Ganglia are connecting the sunstantia nigra to the putamen ( area dopamine is released) and then towards globus pallidus . GT for PD have been administered by drill a hole in each side of patient's skull and injecting the  viral vector in appropiriate doses int the targeted brain region using image-guided surgical techniques.

The treatments usually performed in standard operate room / in radiology suites. The recovery will take time in fast manner where patients usually discharged from ward in 1 / 2 days of GT.

Approach of GT for PD

1.  Increase dopamine production in specific area of brain. 
2. Adjust the pathway of ecitatory and inhibitory of the patient's brain.
3. Using growth factor to protect the progression of PD

                      Gene therapy for PD by Weill Cornell Brain and Spine Center

                        Gene therapy for reversing Parkinson Disease by CBS news