On Rare Disease Day, February 28, attention turns to conditions that are individually rare but collectively affect many families. At Bielefeld University, several research groups are investigating forms of rare diseases, in particular so-called lysosomal storage disorders. The findings from Bielefeld are opening up new perspectives—not only for rare conditions, but also for common diseases such as Parkinson’s disease and dementia.
Key facts at a glance:
• February 28 is Rare Disease Day. Researchers at Bielefeld University are studying these conditions.
• As a group, these disorders affect around 1 in 8,000 newborns and are therefore not as rare overall as the name suggests.
• Research in Bielefeld is providing important therapeutic approaches, also with regard to common neurodegenerative diseases such as Parkinson’s disease and dementia.

“Rare diseases are not a marginal topic for us, but a key to understanding fundamental biological processes,” says Professor Dr. Michael Schwake of Bielefeld University. Together with colleagues, the biochemist investigates genetically caused disorders in which tiny changes in the genome have severe consequences.
Researchers in Bielefeld are working, for example, on rare so-called lysosomal storage disorders. Lysosomes are the “recycling centers” of our cells: specialized enzymes break down large molecules into their building blocks. If one of these enzymes is missing, degradation products accumulate and cells lose their function. Nerve cells are particularly sensitive, as they can hardly regenerate.
When cellular recycling fails
One of these disorders is Gaucher disease. In this condition, the enzyme glucocerebrosidase is compromised. As a result, certain degradation products accumulate in macrophages, which invade into organs such as the liver and spleen. Enzyme replacement therapy exists for some forms. However, other variants affect the nervous system and are still difficult to treat. “What is intriguing is that a reduced activity of this enzyme is also linked to Parkinson’s disease,” explains Schwake. “If we understand how to activtate the enzyme, this may open up new avenues for certain Parkinson’s patients.”
His research group is focusing on so-called chaperones—molecular “folding assistants” that stabilize faulty proteins. Modern gene therapies are equally important. Some approaches use viruses as delivery vehicles to introduce healthy genes into cells. Other strategies specifically intervene in gene regulation and correct faulty genetic instructions. Both approaches are initially tested in cell models to demonstrate their effectiveness—a so-called proof of concept.
Biochemist Professor Dr. Torben Lübke also studies lysosomal disorders such as fucosidosis and various mucopolysaccharidoses. Worldwide, only a few hundred cases of fucosidosis have been documented. “Many children initially develop normally and then lose acquired abilities,” he reports, while others are already severely affected at birth. His research group is deciphering the molecular causes and testing therapeutic approaches in model systems with the long-term goal of translating them into clinical application.
From ultra-rare to widespread
Professor of Biochemistry Dr. Markus Damme focuses on genes such as TMEM106B and GRN. Mutations in these genes lead to ultra-rare lysosomal disorders. At the same time, more common variants increase the risk of frontotemporal lobar degeneration—the second most common form of dementia after Alzheimer’s disease. “If we understand the function of these proteins, we also gain a better understanding of why nerve cells degenerate in dementia,” says Damme.
All of these projects show that “rare” does not mean insignificant. Understanding rare diseases often means better understanding the mechanisms of common diseases as well, thereby creating hope far beyond the small group directly affected. In the Ostwestfalen-Lippe region, patients also benefit from specialized institutions such as the Epilepsy Center at the Evangelisches Klinikum Bethel, part of the OWL University Hospital of Bielefeld University, which provides comprehensive long-term care for patients and their families.

Statement by Professor Dr. Michael Schwake
“What makes this research so special is its dual relevance: We are working on diseases that are dramatic for individual families and urgently require new therapies. At the same time, we are gaining insights that extend far beyond these rare diagnoses. The fact that we bring together several research groups in Bielefeld with different perspectives sends a strong signal for the region and for the international research community.”