Objectives

Parkinson's disease is a complex brain disorder that leads to various movement problems. This occurs because brain cells responsible for dopamine production die off. A protein called LRRK2, which is often overactive in this process, has harmful effects on these cells. On the other hand, there is also a protein, PP2A, that can reduce the harmful effects of LRRK2, but in patients with Parkinson's, this protein functions less effectively.

In our research, we have several clear objectives:

• Understanding the collaboration between PP2A and LRRK2We want to know how these proteins behave in brain and immune cells.
• Activating PP2AWe are looking for ways to activate PP2A with small molecules, also known as SMAPs (Small Molecule Activators of PP2A).
• Testing treatment optionsWe want to investigate whether this activation can protect brain cells from damage in cell models.

If our research is successful, this could lead to new treatment strategies for Parkinson's. We aim to restore the activity of PP2A, with the goal of reducing the harmful effects of LRRK2.

Research details

Our research is divided into three work packages:

Work Package 1: How do PP2A and LRRK2 work?

• We investigate how these proteins work together in brain cells and immune cells.
• For this, we use blood samples from Parkinson's patients and cultured mouse neurons.
• We are also looking at how these proteins respond to harmful conditions, such as alpha-synuclein accumulations, which are characteristic of Parkinson's.

Work Package 2: Study of patient samples and stem cells

• We are investigating the levels of PP2A and LRRK2 present in brain and blood samples from Parkinson's patients.
• We use stem cells (iPSCs) from patients to mimic brain and immune cells.
• Next, we compare the behavior of these cells with that of healthy individuals.

Work Package 3: Testing of PP2A-activating medicines

• We are testing the effectiveness of PP2A-activating drugs (SMAPs) in brain and immune cell models.
• We want to see if these medicines can protect neurons against damage caused by LRRK2 and alpha-synuclein.
• We collaborate with RAPPTA Therapeutics, a company focused on the development of PP2A-targeted medicines.

Desired results

We hope to confirm that PP2A plays a key role in the regulation of LRRK2 in Parkinson's. The goal is to discover new ways to restore PP2A activity in Parkinson's models. We also want to test whether certain medications (SMAPs) can be effective as a potential treatment. If these medications are effective, they might be able to slow the disease process and offer new opportunities for patients.

Significance for patients, researchers, and funders

For patients and caregivers, this research could lead to a new treatment that works differently from current dopamine therapies. Instead of merely combating symptoms, this approach focuses on protecting brain cells.

For scientists and physicians, this study offers new insights into how Parkinson's develops. This could lead to therapies targeting PP2A regulation. For investors and pharmaceutical companies, this research can lay the foundation for clinical trials of PP2A-targeted drugs. The collaboration with RAPPTA Therapeutics demonstrates the industry's interest in this new treatment approach.

This research has the potential to change the treatment of Parkinson's. Not only can the symptoms be relieved, but the disease process itself could also possibly be slowed down.

How can you help?

Without the support of people like you, we cannot continue our research. A donation helps us support groundbreaking research and create new opportunities for patients. Will you join us?

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