Side effects of Parkinson’s treatment reduced by blocking brain protein

Targeting p11 protein in dopamine-responsive region of the brain shows promise in mouse model of Parkinson’s disease.

Researchers say targeting the p11 protein in the dorsal striatum could be a promising avenue for treating Parkinson’s disease with fewer side effects. In the image, molecular model of the p11 protein

The primary treatment for Parkinson’s disease is to replace lost dopamine — the cause of its characteristic symptoms. However, this often results in abnormal involuntary movements (dyskinesia), a side effect that can restrict levodopa dosage and, therefore, efficacy. 

Researchers report in PNAS (online, 19 January 2016)[1]
, that blocking a protein called p11 in the dorsal striatum — a dopamine-responsive region of the brain involved in movement — can reduce dyskinesia associated with levodopa or dopamine-receptor agonists in a mouse model of Parkinson’s disease. In addition, even prior to treatment with levodopa, blocking p11 improved motor symptoms in the mice. 

The researchers say that targeting the protein could be a promising avenue for treating Parkinson’s disease with fewer side effects. But they note that such therapies would likely need to be targeted to the dorsal striatum as universal p11 suppression is associated with depression.

References

[1] Marongiu R, Arango-Lievano M, Francardo V et al. Gene therapy blockade of dorsal striatal p11 improves motor function and dyskinesia in parkinsonian mice. PNAS 2016. doi: 10.1073/pnas.1524387113

Last updated
Citation
Clinical Pharmacist, CP, February 2016, Vol 8, No 2;8(2):DOI:10.1211/PJ.2016.20200522