Reducing side effects of dopamine treatment

Neurons that produce dopamine are degraded in Parkinson’s disease. Although replacing dopamine can improve the resulting loss of motor function, such treatments can also produce involuntary movements, or dyskinesia.

Scientists in the journal PNAS investigated the molecular pathways that lead to this dyskinesia in an effort to ameliorate the condition. Because upregulating serotonin can reduce dyskinesia, the authors focused on p11, a cellular scaffold protein that increases the presence of certain serotonin receptors in the brain.

Using mice with brain lesions similar to those found in Parkinson’s disease, the authors injected small viral vectors encoding an RNA molecule that blocks p11 production in the dorsal striatum, a brain region that responds to dopamine.

Despite predictions that blocking p11 would worsen dyskinesia, the treatment improved motor function. When the mice were treated with dopamine, they showed reduced indicators of dyskinesia.

Because p11 is found throughout the brain, the authors note that systemic p11 blockade could produce side effects such as depression, but suggest that blocking p11 in the dorsal striatum alone may offer a potentially viable therapeutic strategy for Parkinson’s disease.

http://www.pnas.org/content/early/2016/01/13/1524387113