2025 Grant Announcement

The PMD Foundation is excited to share a new grant that will support brain organoid research at Case Western Reserve University School of Medicine, led by Dr. Paul Tesar and Dr. Mayur Madhavan. 

The project aims to understand how antisense oligonucleotide (ASO) therapy affects brain cells from PMD patients with genetic mutations that currently exclude them from existing clinical trials. 

While Ionis Pharmaceuticals’ ongoing ASO clinical trial is currently open to patients with duplications of the PLP1 gene, this new research seeks to determine whether the same therapeutic approach might be applicable to other genetic causes of PMD.

As noted in the proposal:

“[The Tesar lab’s previous] work has demonstrated the therapeutic potential of antisense oligonucleotide (ASO) therapy, which is currently in clinical trials with Ionis Pharmaceuticals for patients with PLP1 duplications. While this represents a promising step forward, PMD encompasses a diverse array of PLP1 mutations, including point mutations and splicing errors, which remain underexplored.

To address this, we have pioneered brain organoid technology, creating 3D tissue models from patient-derived cells that mimic the human brain’s architecture and cellular composition. These organoids allow us to test ASO therapies in a controlled laboratory setting. With funding from the PMD Foundation, we aim to test organoids representing patients with non-duplication PLP1 mutations. Our goal is to determine whether ASO therapy can provide therapeutic benefits across a broader spectrum of PMD mutations, paving the way for more inclusive treatment strategies.”

We wish to extend our thanks to Dr. Paul Tesar and Dr. Mayur Madhavan for their research and look forward to sharing more with our members as the study progresses.