Parkinson's disease: are we treating or crippling?
As part of the joint work, scientists from the Mayo Clinic and the University System of Medical Research of the North Coast, working under the leadership of Demetrius Maraganore, received genetic and clinical evidence that treatment methods that directly affect the expression of the alpha-synuclein protein involved in the development and progression of Parkinson's disease, instead of a positive effect on the condition of patients, can on the contrary, it provokes the progression of the disease and increases the risk of developing physical disability and dementia.
Alpha-synuclein protein is the main component of Levi's bodies – protein aggregates formed in the brain tissue, which are a characteristic feature of Parkinson's disease. Since its discovery as the cause of the development of the familial form of this common neurodegenerative disease, for almost 20 years alpha-synuclein has been the focus of attention of specialists studying its role in the pathogenesis of the idiopathic form of Parkinson's disease, as well as its possible use as a therapeutic target. Many studies have been devoted to the development of molecules that suppress the activity of this protein. A vaccine directed against alpha-synuclein (which reduces its content in brain tissue) is currently undergoing phase I clinical trials, and a number of molecules whose action is also aimed at reducing the expression of this protein are in the last stages of preclinical development.
The authors demonstrated for the first time that, while increased expression of alpha-synuclein increases the risk of developing Parkinson's disease, its reduced expression is unexpectedly associated with worse prognoses for the preservation of motor and cognitive functions after the manifestation of the disease. This observation raises the question of the efficacy and safety of therapeutic approaches aimed at reducing the expression of alpha-synuclein in Parkinson's disease.
As part of the study, scientists monitored the condition of 1,098 patients at the Mayo Clinic for almost 15 years (the average follow-up period was 8 years). The DNA of the patients was sequenced to identify genetic variants regulating the synthesis of alpha-synuclein. The authors analyzed the relationship between these genetic variants and the duration of periods during which patients did not have severe motor and cognitive impairments. The condition of the patients was assessed during telephone interviews.
It turned out that the genotype characterized by reduced expression of alpha-synuclein was characterized by a 23% higher risk of developing dementia and loss of the ability to move independently (the appearance of dependence on a wheelchair).
According to the authors, this work is the first major genetic associative study of the relationship between the expression of alpha-synuclein and the long-term consequences of the development of Parkinson's disease. Reproducing the results obtained in the future should make serious adjustments to the work on new approaches to the treatment of this disease.
The results of the work were discussed at the annual congress of the American Academy of Neurology held on March 18-23, 2013 in San Diego.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Mayo Clinic:
Research Shows Genetic Evidence that New Therapies Targeting Parkinson's Disease may Cause Harm.
22.03.2013