Grateful for the outstanding team effort—especially first co-authors Bara’a Abu Diab and Carlo Manenti, and to Dr. Srinivasarao Repudi, Sara Abu Swai, Dr. Rania Akkawi and Takwa Jebara for their important contributions, and to Dr. José Dávila-Velderrain for his invaluable collaboration.

WWOX stabilizes SOX10 to promote maturation into myelinating oligodendrocytes, while its loss traps OPCs in a non-differentiating state and impairs repair. These findings position the WWOX–SOX10 axis as a promising therapeutic target for MS and other demyelinating diseases.

Kudos to Osama Hidmi and thanks to Pei-Chi Wei for the great collaboration.

This study not only deepens our understanding of WWOX’s role in cortical development but also sets the stage for targeted therapeutic strategies for these rare but impactful disorders.

We’re thrilled to contribute to the growing intersection of iPSC-derived models, neuroscience, and gene therapy.

Our work also highlights key differences between WOREE and SCAR12 syndromes, with SCAR12 showing milder phenotypes and RG/neuron profiles closer to wild-type, correlating with the milder clinical presentation.

2. Increased MYC expression, potentially mediated by Wnt signaling, leading to hyperexcitability and delayed neuronal maturation.

3. Importantly, we demonstrate the potential of AAV9-mediated WWOX gene therapy in reversing these deficits, offering new hope for treating WWOX-related disorders.

Using advanced iPSC-derived neural organoid models and comprehensive omics approaches, we identified that WWOX deficiency is associated with:

1. Disruption in radial glial (RG) cell populations and dysregulated cell cycle dynamics.

A fantastic collaboration with the José Davila-Velderrain’s group at Human Technopole and Shani Stern’s group at the University of Haifa. Huge congratulations to Daniel Steinberg and Asia Zonca for their outstanding contributions!

What did we find?