Gene therapy shows promise in Parkinson's disease
options for patients with Parkinson's disease has been published
this week, which could bring hope to more than 1 million Americans
each year who suffer from this neurodegenerative disorder.
The researchers found that viral delivery of a gene associated with Parkinson's disease protected neurons from degeneration. This was tested by injecting rats sub-cranially with lentiviral vectors containing the genes for Parkin's, a recessive form of inherited Parkinson's disease, as well as a mutated form of the alpha-synuclein gene.
Researchers use harmless forms of viruses such as the lentiviral vector because they can efficiently penetrate cells and deliver the gene of interest without inducing a major immune response.
One form of inherited Parkinson's is associated with mutations in the alpha-synuclein gene that cause overexpression of the alpha-synuclein protein. Alpha-synuclein, in turn, is a major component of brain deposits that are characteristic of sporadic Parkinson's. This suggests that the disease might be linked to a toxic overaccumulation of alpha-synuclein.
The findings constitute a significant step forward in understanding the molecular mechanisms behind the disease. This latest discovery, made by Scientists at the Ecole Polytechnique Federale de Lausanne (EPFL) in Lausanne, Switzerland, also demonstrates the first time the feasibility of the gene therapy approach in a genetic model of Parkinson's disease.
Results of this research could also lead to new treatments that could prevent the onset of Parkinson's disease in genetically predisposed subjects and arrest the disease's progression once it has been diagnosed.
EPFL President Patrick Aebischer, who led the research team said: "These observations could translate into the clinic either through a direct gene therapy approach or through the identification of small drugs which enhance the expression of the endogenous parkin."
Parkinson's disease is a progressive, degenerative neurological disorder in which dopamine-producing neurons in the part of the brain responsible for coordinating muscle movement die or become so damaged that they are no longer able to function.
Dopamine is a neurotransmitter, a "chemical messenger" that transfers information from neuron to neuron, ultimately allowing us to use our muscles in a smooth, coordinated way. Disease symptoms, such as tremor, rigidity, difficulty coordinating movement and difficulty with balance, begin to manifest themselves when about 80 per cent of a victim's dopamine-producing neurons have died.
Scientists estimate that Parkinson's disease affects 1-3 per cent of people over the age of 60. In the United States alone, 1.5 million people suffer from Parkinson's disease, and about 60,000 new patients are diagnosed every year. Although it is commonly thought of as a disease of the elderly, 15 per cent of Parkinson's victims are under the age of 50.
The cause of Parkinson's disease is currently unknown and there is no way to prevent its onset and once diagnosed, it has no cure. Treatment is limited to ameliorating symptoms with a variety of therapies, including dopamine-based drug therapy.
Only about 5-10 per cent of Parkinson's appears to be inherited, and to date five genes have been implicated in patients with a familial history of the disease. Studies of these inherited forms of Parkinson's have led to insights on its pathogenesis in sporadic or non-inherited cases.
The research is to be published this week in the Proceedings of the National Academy of Sciences.
