A protein accumulation similar to Parkinson’s disease can also be seen in Alzheimer’s disease and other dementias where b-amyloid forms plaques and Tau protein forms aggregates within the cells, called neurofibrillary tangles. The current view is that the formation of Tau aggregates eventually leads to neuronal death, and Tau accumulation correlates well with clinical symptoms. Tau is particularly important for dementias called Tauopathies that include e.g. frontotemporal dementia.
In a freshly published paper, Professor Timo Myöhänen’s group from the Universities of Helsinki and Eastern Finland showed that a PREP inhibitor reduces Tau accumulation and toxicity also in the cellular models, including patient-derived neurons from frontotemporal dementia patients.
After promising cellular results, PREP inhibitor treatment was also tested in a mouse model of frontotemporal dementia. To follow the clinical situation, one month treatment with the PREP inhibitor was initiated by the time of memory impairment. After treatment, mice that received the control treatment were performing poorly in a memory test, but mice treated with the PREP inhibitor had normal cognitive skills.
“Our most important discovery was that the PREP inhibitor treatment had reduced Tau accumulation in the brain areas related to cognition and memory, also leading to reduced oxidative stress markers that are common in neurodegenerative diseases,” says Professor Timo Myöhänen.
“The results from the memory tests after PREP inhibitor treatment were surprisingly good, as treatments in similar studies are usually initiated before the symptoms, not after symptom onset. This supports the further development of PREP-targeting drugs, and we are currently looking for investors or collaborators for this”, Professor Myöhänen says.
The research was mainly performed in Professor Myöhänen’s research groups at the Universities of Helsinki and Eastern Finland, and groups from Harvard University, USA, and the University of Heidelberg, Germany, also participated in the study.
- A prolyl oligopeptidase inhibitor reduces tau pathology in cellular models and in mice with tauopathy, Science Translational Medicine,12 Apr 2023,Vol 15, Issue 691