VIB Scientists develop a new strategy to restore enzyme functionality ​ in Parkinson's disease 

Nanobody technology might restore the function of an enzyme involved in, among others, Parkinson's disease.

Brussels, 27 May 2025 – Researchers at the University of Padova (Italy), the VIB-VUB Center for Structural Biology and the Vrije Universiteit Brussel have used nanobody technology to restore the function of an enzyme involved in, among others, Parkinson's disease. Their work appears in Nature Communications. 

A dysfunctional enzyme in Parkinson’s disease 

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and it affects more than 10 million people globally. With no current cure, the progressive condition leads to motor dysfunction, balance issues, and in some cases in later stages to dementia. While the exact causes of PD remain unclear, a key risk factor is the malfunction of the enzyme glucocerebrosidase (GCase), responsible for breaking down specific lipids. Mutations in the GCase gene impair the enzyme’s normal function, which results in cellular waste accumulation and cellular dysfunction. 

Structure of GCase (blue) in complex with a stabilizing nanobody (yellow).

Using nanobodies 

To address this, the teams of Prof. Wim Versées (VIB-VUB) and Prof. ​ Nicoletta Plotegher (University of Padova) developed an innovative approach based on Nanobodies® – small, stable fragments of antibodies naturally found in camelids – to enhance the function of GCase. Traditional molecular chaperones (molecules that bind to GCase to improve its function) often block the enzyme’s active site and thereby limit their effectiveness. In contrast, the newly developed nanobodies bind to GCase in an alternative way and far from the active sites. This mechanism stabilizes or activates GCase without interfering with its natural role. 

New routes ahead 

“Our nanobodies offer a completely new way to modulate GCase function” says Prof. Versées (VIB-VUB). “We were able to show that certain nanobodies can significantly enhance GCase function in cellular models and even improve the activity of mutant GCase variants known to cause disease.” 

These promising findings highlight the power of international collaborations in tackling complex neurological diseases and showcase the potential of nanobody technology to lay the groundwork for future therapeutic strategies. ​ 

Dr. Thomas Dal Maso, the main researcher performing this work at the Versées lab, adds: “To translate these nanobody-based tools into targeted treatments for patients, more research is needed, particularly in developing methods to deliver them effectively to affected brain cells.” ​ 
Dr. Thomas Dal Maso and Prof. Wim Versées

Publication 

Developing nanobodies as allosteric molecular chaperones of glucocerebrosidase function. Dal Maso, Sinisgalli, et al. Nature Communications, 2025. 

Funding 

This work was supported by the Michael J. Fox Foundation for Parkinson’s Research, FWO, and VUB. 


Gunnar De Winter

Gunnar De Winter

Science Communications Expert, VIB

 

 

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VIB is an independent research institute that translates insights in biology into impactful innovations for society. Collaborating with the five Flemish universities, it conducts research in plant biology, cancer, neuroscience, microbiology, inflammatory diseases, artificial intelligence and more. VIB connects science with entrepreneurship and stimulates the growth of the Flemish biotech ecosystem. The institute contributes to solutions for societal challenges such as new methods for diagnostics and treatments, as well as innovations for agriculture. 

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