Preventing Parkinson’s: Award for an innovative vaccine approach

Professor Chi Wang Ip and Assistant Professor Rhonda Mc Fleder from the Department of Neurology at Würzburg University Hospital (UKW) are attempting to develop a preventive vaccine against Parkinson’s disease. Professor Mathias Munschauer from Heidelberg University Hospital, a Würzburg alumnus, is also involved in the project.

The team’s concept and initial work have impressed the Parkinson’s Foundation: their project was awarded the Foundation’s Manfred Moggert-Kemper Innovation Prize, worth 100,000 euros, in the newly introduced ‘Prevention’ category.

However, in the case of Parkinson’s, there is no pathogen against which a vaccine could be directed. So how does the concept work?

“Whilst traditional vaccines train the immune system to better ward off or fight viruses, with our vaccine we aim to specifically train the immune system to suppress potentially harmful immune reactions,” explains Chi Wang Ip. “In our case, with Parkinson’s disease, the aim is for the immune system to become tolerant to certain forms of the body’s own protein, alpha-synuclein.”

The alpha-synuclein protein is found on nerve cells. In patients with Parkinson’s, it is altered and subsequently activates the immune system.

As a result, immune cells in the brain become overactive, leading to inflammation. This damages the dopamine-producing nerve cells – and the resulting dopamine deficiency is responsible for the typical symptoms of Parkinson’s disease: slowness of movement, muscle stiffness and tremors. The aim, therefore, is to preserve the nerve cells that produce dopamine.

Chi Wang Ip is Professor of Translational Neurology and Deputy Director of the Department of Neurology at Würzburg University Hospital. Here, together with Assistant Professor Rhonda McFleder, a doctor and biologist, he is researching the neuroimmunological mechanisms underlying Parkinson’s disease. Professor Mathias Munschauer , an expert in RNA viruses, is Director of the ‘Molecular Virology’ department at the Centre for Infectiology at Heidelberg University Hospital. Prior to this, he headed a research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg.

Special mRNA protected dopamine-producing nerve cells

Using a specially developed mouse model that mimics Parkinson’s disease, the research team has already demonstrated that the administration of a specially developed mRNA promotes targeted immune tolerance against alpha-synuclein.

The treatment protected dopamine-producing nerve cells, preserved important neural connections in the brain and reduced the infiltration of CD8 T-cells into the brain. Furthermore, the number of regulatory T-cells (Tregs) in the blood increased. Tregs can curb immune responses and prevent excessive immune reactions.

“However, the treatment was unable to fully protect the nerve cells. This suggests that the therapeutic window may already be limited once the inflammatory and neurodegenerative cascade has begun. We therefore now want to intervene at an earlier stage and try to prevent Parkinson’s disease with an mRNA-based vaccine,” says Rhonda McFleder.

Acclimatising the immune system to alpha-synuclein at an early stage

In what is known as ‘tolerogenic mRNA vaccination’, selected components of the alpha-synuclein protein are presented to the immune system using modified mRNA molecules encapsulated in tiny lipid particles.

“If we accustom the immune system to it at an early stage, we could prevent harmful immune reactions and inflammatory processes in the brain, or at least significantly reduce them, thereby slowing down or even preventing the loss of dopamine-producing nerve cells,” says Mathias Munschauer, outlining the team’s hypothesis.

Further optimising and testing the mRNA vaccine

With funding from the Parkinson’s Foundation, the team aims to further optimise the composition of the mRNA vaccine and test its preventive effect in two mouse models with different disease progression patterns.

“In doing so, we also want to find out which immune mechanisms underlie this effect and which biological indicators might help in the future to identify people at increased risk of Parkinson’s at an early stage,” summarises Chi Wang Ip.

Vaccinations are among the greatest successes of preventive medicine. Not only can they prevent infectious diseases such as flu or COVID-19, but they can also avert serious complications and long-term damage. For example, the HPV vaccine reduces the risk of cervical cancer by up to 90 per cent. The measles vaccine prevents a dangerous loss of immune defences and protects against encephalitis, which can lead to permanent brain damage or death. And the polio vaccine can prevent inflammation of the central nervous system as well as irreversible paralysis. These examples show that a preventive immunological intervention can prevent subsequent irreversible tissue damage, provided the underlying cause is known.