A research team at the University of Helsinki has succeeded in correcting the motor symptoms associated with Parkinson’s disease. This could revolutionise its treatment in future.
A research team led by Docent, Doctor of Pharmacy Timo Myöhänen has achieved promising results in terms of the treatment of Parkinson’s disease.
“Of course, it will still take a long time before the medicine is available in pharmacies. But the results are encouraging for pharmaceutical development.”
Parkinson’s disease is caused by the destruction of the nerve cells in the brain, but the exact cause of the disease is not known. The symptoms include tremor, limited movement and stiff muscles. About two per cent of over 60-year-olds suffer from Parkinson’s.
“Parkinson’s disease is only diagnosed once the clinical symptoms are present, and by that time half of the nerve cells have already been damaged. The current pharmaceutical care does not rescue the destroyed cells or halt the progress of the disease.”
The research team wanted to find out whether it was possible to prevent the progressive cellular destruction.
“A protein called alpha-synuclein has several functions in the brain, but in Parkinson’s disease these proteins start to aggregate. The resulting accumulations damage cells and spread. This can be a critical point in the development of the disease.”
Effective PREP blockers
In his doctoral dissertation from 2008, Myöhänen studied an enzyme called prolyl oligopeptidase, or PREP. PREP had earlier been associated with degenerative diseases, but the mechanism was unclear. The same year, a Belgian research team proved with an in vitro model that PREP increases protein accumulations.
After Myöhänen had transferred from Kuopio to work as a researcher in Helsinki, he started to test how compounds that inhibit PREP affected the accumulations in cellular and animal models. Later and more detailed analyses showed that the PREP blocker had cleared the animals’ brains of nearly all harmful accumulations.
In his latest study, Myöhänen's team 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. Motor symptoms started to appear in two to four weeks.
“At four weeks, we started the PREP blocker treatment. In this way, we tried to imitate a real situation. The symptoms disappeared in two weeks and did not reappear until after the experiment was over. The amount of protein accumulations decreased substantially. In other words, we managed to target the root cause of the disease.”
A new compound under development
In animal models, the treatment is usually started right away, but Myöhänen and his team waited for the symptoms to appear. The PREP blocker treatment not only stopped the motor areas from becoming further damaged but also cleared the brain of nearly all accumulations.
“We were astounded by the rapid results. And PREP blockers are of low molecular weight, which will make their further development easier.”
In this study, the researchers used an existing model compound but they will develop a new compound to be patented. Myöhänen hopes that pharmaceutical companies will be interested, as this sort of research would make an excellent cooperation project.
“It would be great to find a new solution for Parkinson’s disease. No treatment will bring the dead nerve cells back, but at least we might be able to delay the progress of the disease.”
Text TARJA VÄSTILÄ
Images VESA TYNI