In observance of Rare Disease Day, the Biofisika Institute (CSIC, EHU) is disseminating updates on a research initiative dedicated to elucidating the molecular underpinnings of CTNNB1 neurodevelopmental syndrome. This rare condition arises from alterations in the beta-catenin protein. While fewer than fifty instances of this pathology have been identified in Spain, rare diseases collectively impact close to three million individuals.
The investigative efforts are spearheaded by Sonia Bañuelos, a researcher affiliated with the Biofisika Institute and an academic within the Department of Biochemistry and Molecular Biology at the University of the Basque Country (EHU).
“Our primary objective is to comprehend the manner in which these genetic anomalies impede the correct formation of the brain. A thorough understanding of the underlying mechanisms at a molecular scale is indispensable for the eventual formulation of targeted therapeutic interventions,” the scientist stated.
This project is being conducted through cooperative partnerships with a neuropsychology cohort from the University of Deusto – a leading institution in the study of this condition – molecular geneticists from the Biobizkaia Institute at Cruces University Hospital, and the brain organoid facility at the Achucarro Neuroscience Center. Furthermore, the Spanish Association of CTNNB1 Patients, headquartered in Bizkaia, is an active participant in this endeavor.
A Crucial Protein for Optimal Brain Development
Beta-catenin plays a vital role throughout embryonic development and continues to be essential in the adult organism. Among its functions is its involvement in cell adhesion, which contributes to the structural integrity and mechanical resilience of tissues. These processes are paramount during the intricate stages of brain formation and in the establishment and adaptability of synapses, which form the foundation of cognitive functions such as learning and memory.
In the context of CTNNB1 syndrome, a majority of identified mutations result in the production of truncated or improperly folded proteins that are incapable of fulfilling their designated roles. This functional deficit disrupts critical developmental pathways within the brain.
Leveraging AI, Biophysics, and Brain Organoids for Rare Syndrome Investigation
The research team at the Biofisika Institute employs advanced computational tools that analyze the three-dimensional architecture of proteins. These tools are used to predict the consequences of specific mutations on the interaction between beta-catenin and cadherin, which are integral components of cell adhesion complexes.
These predictive analyses are subsequently subjected to rigorous experimental validation using biophysical methodologies. To achieve this, modified versions of the protein, mirroring those found in actual cases identified within the Spanish patient population, are synthesized in bacterial systems. The utilization of brain organoids facilitates a more accurate simulation of how these molecular alterations influence the developmental trajectory of neural tissue.
“While this constitutes fundamental research, the findings hold the potential to inform the future development of rationally designed therapeutic strategies,”
Sonia Bañuelos, Researcher, Biofisika Institute and Lecturer, Department of Biochemistry and Molecular Biology, University of the Basque Country
Advocating for Research into Rare Diseases
“Gaining insight into the etiological mechanisms of a disease represents the initial indispensable step toward discovering a cure. Consequently, robust research into rare diseases is not merely beneficial but essential,” the researcher emphasized.
On this notable occasion of Rare Disease Day, the Biofisika Institute reiterates the critical importance of fostering research endeavors into these less prevalent conditions, acknowledging their profound and often life-altering impact on affected individuals.
