People with Parkinson’s disease commonly suffer a slowing or freezing of movement caused by the death of neurons that make dopamine, a key chemical that allows brain cells to send and receive messages essential to voluntary movements.
Patients regain the ability to move, seemingly miraculously, by taking L-DOPA or related drugs that mimic the missing dopamine.
After a few years on L-DOPA, however, most patients again lose motor control — but in an opposite way. Instead of too little, there is too much movement, like involuntary nodding and rocking — side effects known as L-DOPA-induced dyskinesias.
A new MIT study identifies two related genes linked to L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease. The expression of these two related CalDAG-GEF genes is altered in opposite ways in the striatum brain region of animals with dyskinesias.
The results may lead to new approaches to the treatment of dyskinesias in Parkinson’s patients.
“L-DOPA-induced dyskinesias are a major problem for patients, and there is a great need to help with these drug side effects,” said MIT Institute Professor Ann Graybiel, a prominent Parkinson’s researcher at the McGovern Institute for Brain Research at MIT.
Graybiel and her colleagues have identified two molecules whose expression in the brain is altered in the brains of animals with L-DOPA-induced dyskinesias. The results may lead to new approaches to the treatment of dyskinesias in Parkinson’s patients, of which there are more than 1 million in the United States alone.
“We’re very excited because these genes are concentrated in precisely the places that lose dopamine in Parkinson’s disease, so they might be reasonable targets to go after therapeutically,” Graybiel said.
This research was published in the advance online issue of Proceedings of the National Academy of Sciences.