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Breakthrough in Parkinson’s treatment: the drug stops the disease progression

The scientists at the University of Colorado School of Medicine revealed the drug which activates the gene preventing Parkinson’s disease. The experiments showed that it stops the pathology progression in mice. Now the drug is tested as Parkinson’s treatment in humans.

Currently used therapy fights only the symptoms but it doesn’t stop the progression of the disease. The researchers discovered that the drug phenylbutyrate prevents the development of Parkinson’s. The drug activates the gene called DJ-1, which protects the dopamine neurons in the brain. It may be used in Parkinson’s treatment as the disease is caused by the destruction of dopamine brain cells.

The gene DJ-1 enhances the production of antioxidants such as glutathione to neutralize the harmful impact of excess oxygen to neurons. Besides, DJ-1 helps to remove abnormal proteins which accumulate in the cell causing its death. Dopamine neurons are especially sensitive to excess oxygen and aggregation of abnormal proteins.

The researchers investigated the DJ-1 gene since 2003 when it was discovered that mutations in this gene may lead to Parkinson's disease. For several years they studied the role of the gene in cell functioning. The scientists had to find an agent able to turn on the gene DJ-1 to create medication for Parkinson’s treatment. It was known that some molecules are able to activate particular genes. For instance, testosterone turns on genes in muscle cells responsible for buildup of muscle mass.

After testing many agents, the researchers found that phenylbutyrate could activate DJ-1 and prevent the death of dopamine neurons. They added the drug to drinking water of mice genetically programmed to become parkinsonian with age. The abnormal proteins didn’t accumulate in the brain cells of mice receiving phenylbutyrate.

The animals moved normally and demonstrated no changes in their mental function. But the mice not receiving the drug gradually lost their ability to move as their dopamine neurons were killed by the Parkinson's disease. The researchers started to test phenylbutyrate in humans as Parkinson’s treatment in 2009. The results of the study will be published in the nearest future.

The research leads to creating the medication which will turn on the DJ-1 gene and stop the progression of Parkinson's disease. Existing drugs like L-DOPA increase dopamine production in the brain but cannot prevent the death of neurons. The one disadvantage of the phenylbutyrate is that the patients need large doses, 16 grams per day or 32 large tablets taken frequently. The scientists are now searching for other agents able to activate the DJ-1 gene.