Neurodegenerative diseases are a global problem that grows as the population ages. Parkinson’s disease affects 6 to 10 million and Alzheimer's disease more than 50 million people. Neurodegenerative diseases have no therapies that would modify the course of the disease by stopping or even slowing down the progressive neuronal destruction. As a result, the patient’s condition worsens as the disease progresses, and the effect of pharmacotherapies decreases, for example, in patients with Parkinson’s disease. Once nerve cells are destroyed, treatment is no longer possible.
Experimental disease-modifying therapies for Parkinson’s disease and Alzheimer’s disease have so far been unsuccessful in clinical trials. Prior therapies have been primarily targeted at individual disease mechanisms.
Small molecules developed by the NeuroPREP research group at the at the University of Helsinki, which regulate the prolyl oligopeptidase (PREP) enzyme, have a new and simultaneous effect on a number of disease mechanisms. These new molecules are expected to stop, or at least slow down, the destruction of neurons and the worsening of the patient’s symptoms.
“PREP ligands have a positive effect on a number of disease mechanisms associated with several neurodegenerative diseases. The compounds have restored normal mobility in mice in an animal model of Parkinson’s disease, while normal learning functions were restored in an animal model of Alzheimer’s disease. Disease-modifying therapies are needed, and the PREP ligands developed by my group at the University of Helsinki show potential,” says Professor Timo Myöhänen from the University of Eastern Finland.
The discovery of the compound type is based on long-standing investigations into the function of the PREP enzyme. PREP is an intracellular protein that occurs in the brain and elsewhere in the body, which has been found to accelerate harmful functions that promote neurodegenerative diseases, such as the aggregation of harmful proteins and cellular oxidative stress. Previously, the NeuroPREP group investigated a range of PREP inhibitors, which aim to inhibit the function of the enzyme. However, the group’s latest findings show that previously developed PREP inhibitors are not the best possible compounds to inhibit these adverse mechanisms in models of neurodegenerative diseases.
The ligands discovered as a result of 12 years of basic research are entirely new and based on a new functional principle and binding site in the PREP enzyme. In addition, they affect, through a single target, the aggregation and digestion of misfolded proteins, oxidative stress, and other disease mechanisms commonly associated with neurodegenerative disease.
The project has been headed by Professor of Pharmacology and Drug Development Timo Myöhänen and Docent of Pharmaceutical Chemistry Erik Wallén. Professor Myöhänen has focused on supervising the pharmacological investigations focused on PREP and compound testing, while Docent Wallén has been responsible for the project’s pharmaceutical chemistry element. Over the years, more than 20 people have contributed to the project, producing more than 20 publications, three invention disclosures and one patent application, which would not have been possible without long-term basic research.
The research group aims to conduct a short-term further study comparing the optimised PREP ligands with current therapies. The next stage will be preclinical trials followed by clinical trials where the PREP ligand will be first tested on healthy volunteers and then on a small group of patients. If the initial trials are successful, they will be expanded to a larger group of patients. The goal is to obtain an effective treatment that slows down or even stops disease progression, which could be applied to several neurodegenerative diseases.
The research group aims to conduct a short-term further study comparing the optimised PREP ligands with current therapies. The next stage will be preclinical trials followed by clinical trials where the PREP ligand will be first tested on healthy volunteers and then on a small group of patients. If the initial trials are successful, they will be expanded to a larger group of patients. The goal is to obtain an effective treatment that slows down or even stops disease progression, which could be applied to several neurodegenerative diseases.
This commercialisation project funded by Business Finland has ended.
Neurodegenerative diseases are a global problem that is growing as the population ages. Parkinson’s disease affects 6 to 10 million and Alzheimer’s disease more than 50 million people. In the case of neurodegenerative diseases, there are no therapies that would modify the course of the disease by stopping or even slowing down the associated progressive neuronal destruction.
Compounds developed by researchers at the University of Helsinki that regulate the PREP enzyme have a new and simultaneous effect on a number of disease mechanisms. These new molecules are expected to stop, or at least slow down, the destruction of neurons and the worsening of the patient’s symptoms.
Pharmaceutical industry or investors in a startup whose aim is to take the compounds into clinical trials.
Webpage for PREP in Neurodegenerative Disorders research group
Professor Timo Myöhänen, timo.myohanen@helsinki.fi