Federal Minister Eva-Maria Holzleitner presented the 2024 Austrian State Prize for the Promotion of Alternative Methods to Animal Experiments to Catarina Martins-Costa, Nina Corsini, and Jürgen Knoblich for their publication "ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum", published in the journal Cell Stem Cell in 2024.
In the awarded study, conducted in collaboration with Yoshiho Ikeuchi’s lab at the University of Tokyo, the team developed the first in vitro model of the human corpus callosum, a thick nerve bundle connecting the brain’s left and right hemispheres and enabling communication between distant regions for complex cognitive functions.
In very rare cases, this connection fails to form during development, a condition known as corpus callosum agenesis, which can lead to severe impairments in brain function. Roughly ten percent of cases of corpus callosum agenesis are linked to mutations in a gene called ARID1B. However, the lack of suitable models has long limited scientists’ ability to study how ARID1B mutations disrupt corpus callosum formation.
To overcome this limitation, the researchers developed the first in vitro model of the corpus callosum. For this, the team placed two separate brain organoids – small, three dimensional models grown from patient-derived stem cells – close together and studied how they formed connections with each other over time.
“This research was conducted without experimental animals, but exclusively using clinical data and in vitro models,” explains Catarina Martins-Costa, the study’s first author. “In addition, the brain organoids were produced without rodent-derived culture medium.”
Using this model, the team found that organoids derived from patients carrying the ARID1B mutation formed significantly fewer neuronal projections compared to healthy controls. The researchers confirmed that ARID1B mutations alter gene expression and ultimately disrupt the brain’s inability to form long-range connections.
Rethinking Brain Research
This innovative model not only provides insight into the origins of corpus callosum agenesis but also offers the research community a powerful new tool for studying human brain development in vitro, reducing the need for animal testing in neuroscience and beyond.
“Our approach allows us to test drugs directly on human tissue, directly targeting the human disease and ensuring that animal testing is reduced and not done in vain,” comments Jürgen Knoblich. “Our research is only possible because of the excellent conditions at IMBA and the Vienna Biocenter - and because of the support of the Austrian Academy of Sciences. The excellent additional funding from the State of Austria and the City of Vienna has allowed us to establish IMBA as a center for organoid research and make Austria an internationally visible hub for this pioneering technology.”
The State Prize highlights a broader shift in neuroscience towards ethically responsible, human-relevant research approaches that can enhance our understanding of the brain while reducing reliance on animal experimentation.
"We would like to express our sincere thanks for this award, which encourages us to continue working to reduce animal testing,” says Nina Corsini. “While we have learned a lot about the brain through animal experiments in the past, we now have an additional direct insight into the human brain through the brain organoids technique. This allows us to find out how the human brain develops and how diseases such as epilepsy arise.”
About the Austrian State Prize for the Promotion of Alternative Methods to Animal Experiments
With the State Prize for the Promotion of Alternative Methods to Animal Testing, endowed with 10,000 Euro, the Federal Ministry for Women, Science and Research annually recognizes outstanding scientific work whose results or objectives, in accordance with the "3Rs" principle (Replace, Reduce, Refine; Russel and Burch 1959), are the avoidance or reduction of the use of animals in animal testing or the improvement of the conditions for the breeding, housing, care, and use of animals in animal testing.
Further Reading:
News story: First model of the brain's information highways developed
Original Publication: ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum.
Interview with Catarina Martins-Costa: Challenging, yet rewarding
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