Finnish researchers correct Parkinson's motor symptoms in mice

A research group led by University of Helsinki Docent Timo Myöhänen has succeeded in correcting the motor symptoms associated with Parkinson’s disease in mice. These results are promising in terms of treatment, since Parkinson's disease is practically always diagnosed only after motor symptoms appear.

Up to two per cent of people over 60 contract Parkinson’s. The disease causes severe motor symptoms, as it destroys the nerve cells in the brain’s motor areas. The exact cause of the disease is not known, but during the past 15 years research has focused on a protein called alpha-synuclein, which has several functions in the brain areas that regulate motor functions.

This protein is prone to mis-folded forms, which can clump together as aggregates. In Parkinson’s disease, aggregated alpha-synuclein proteins accumulate within nerve cells, damaging them. They can also propagate from one cell to the next and spread the impairment of nerve cells in the brain.

Researchers had previously known that the PREP enzyme, which occurs naturally in the body, can increase the formation of such harmful alpha-synuclein aggregates in the brain. Now researchers wanted to determine the connection that the enzyme and protein have to the symptoms of Parkinson's disease by blocking PREP in the brain.

In the study, Myöhänen’s group set up a mouse model for Parkinson’s disease, in which the brain’s motor areas were made to produce large amounts of alpha-synuclein. This led to the accumulation of mis-folded proteins in the brains of the mice as expected, resulting in the associated motor symptoms.

PREP blockers restore motor skills

The researchers began treatment with a PREP blocker only when the mice began manifesting clear motor symptoms. The situation would be similar in a human case of Parkinson’s which is typically diagnosed only once the symptoms have appeared. Researchers were astounded by the rapid results.

 “After as little as two weeks of treatment, the motor symptoms in the mice had practically disappeared. And they did not reappear until after the experiment was over,” explains Myöhänen.

A detailed analysis established that the PREP blocker treatment had stopped the motor areas from becoming further damaged and had cleared the brain of nearly all accumulations of alpha-synuclein.

 “We have a long way to go from animal models to human trials, but these results are extremely encouraging in terms of future drug development," says Myöhänen.   

The results of Myöhänen’s group have been published in the internationally esteemed  Journal of Neuroscience. Original article: Svarcbahs R, Julku U, Myöhänen TT; ”Inhibition of Prolyl Oligopeptidase restores spontaneous motor behavior in alpha-synuclein virus vector based Parkinson's disease mouse model by decreasing alpha-synuclein oligomeric species in mouse brain”.

Further information

Timo Myöhänen
DPhil (Pharmacy), docent
Division of Pharmacology and Pharmacotherapy
+358 2941 59459
timo.myohanen@helsinki.fi
Twitter @MyohanenTimo
http://blogs.helsinki.fi/prepinneuro/
Alpha-synuclein and an enigma called PREP

Parkinson’s disease is a degenerative disease of the motor system, in which the nerve cells in the brain areas which regulate voluntary movement are destroyed for an unknown reason.  The symptoms may be alleviated with drug treatment, but there is currently no known cure.

Alpha-synuclein is a protein involved in neurotransmission in the brain, for example in the areas that regulate voluntary movements.

Alpha-synuclein is prone to defective structures, and when mis-folded will cling to other alpha-synuclein proteins to form large aggregated pieces which damage brain cells.

Such alpha-synuclein aggregates are particularly common among Parkinson’s disease patients, which has led to alpha-synuclein becoming associated with the onset and progression of Parkinson's.

The PREP enzyme and its function have remained a mystery in previous research, but it has been found to promote the formation of harmful alpha-synuclein aggregates in the brain.

Now researchers have managed to clear the brains of mice of alpha-synuclein aggregates by blocking the PREP enzyme, curing them of the motor symptoms which characterise Parkinson's disease.

The research was funded by the Academy of Finland, the Jane and Aatos Erkko Foundation, the University of Helsinki’s research funding as well as the Sigrid Juselius Foundation.