Grants Awarded

Principal Investigator:
Raphaela Schwentner
St. Anna Children’s Cancer Research Institute,
Vienna, Austria

Date of Award:
December 2025

Amount of Award:
50,000

Layperson Summary:
Langerhans cell histiocytosis (LCH) is a rare disease that mostly affects children. It is a disease that is based on mutations in a specific signaling pathway, the MAPK pathway. In 50-60% of cases a single mutation, called BRAFV600E, is the cause of the disease. LCH can range from a mild illness affecting only one area of the body to a serious condition that impacts multiple organs and requires strong treatment. Most children survive, but some develop long-term problems, especially brain-related damage called neurodegeneration. 

Recent research shows that certain mutated cells may be responsible for this brain damage. These cells can get into the brain, where they may harm nerve cells—even after the initial treatment seems to work. 

In our recent study, we created lab-grown versions of these mutated brain immune cells (called iMicroglia) and nerve cells (iNeurons). We found that the mutated iMicroglia damage the iNeurons and cause them to release neurofilament light, which is a specific marker that signals brain injury. 

In this project, we want to better understand how these mutated cells cause damage in the brain. We’re especially interested in how they interact with neurons and which harmful factors they might release to destroy the neurons. We will also perform drug screenings using our cell model to find new drug candidates.  

Another part of our research involves creating a special zebrafish model of LCH. These fish are transparent, so we can watch how the disease develops in real time. We will label normal and mutated cells with a fluorescent marker, which lets us track them under a microscope. In the future, this zebrafish model will also help us test many different drugs at a time to find ones that might work as treatments. 

If this project is successful, we will have a better understanding of how neurodegeneration in LCH works and thereby will find new treatment options to not only get patients with LCH into remission but also save them from devastating long-term complications.