"We know some drugs can turn on genes. For example, steroids like testosterone act on genes in muscle cells to create muscle bulk," said Freed.
After testing many drugs, the team found that phenylbutyrate could activate DJ-1 and keep dopamine neurons from dying. Next, they put the drug in the drinking water of mice genetically programmed to get Parkinson's disease as they aged.
Aging mice receiving the drug were able to move normally, had no decline in mental function, and their brains did not accumulate the protein that causes Parkinson's. By contrast, older animals that did not get the drug saw a steady decline in their ability to move as their brains were damaged by abnormal proteins.
The researchers began giving phenylbutyrate to people in 2009, to test the safety of the drug in Parkinson patients.
Zhou and Freed will publish the human results in the coming months.
"We look forward to a future when Parkinson patients will be able to take a pill that will turn on the DJ-1 gene and stop the progressive disability associated with the illness," Freed said. "Right now, when you get the diagnosis of Parkinson's, you can expect to have a steady decline in the ability to move. While drugs like L-DOPA are very important for generating dopamine in the brain and making movement possible, these drugs have little impact on the ongoing deterioration of the patients' own brain cells."
Over one million people in the United State have the disease which usually strikes those in their 50s and 60s. Patients have a decline in their ability to walk, talk, and write because of slow movement and rigid muscles. They develop tremors and reflexes slow down. The current treatment of Parkinson's is based on drugs that increase dopamine production in the brain.
Freed is a national leader in transplanting dopamine cells into the human brain to relieve symptoms. He and his n
|Contact: David Kelly|
University of Colorado Denver