We are thrilled to share that scientists at our laboratory have identified a potential explanation as to why the nervous system fails to repair itself in people with progressive MS.

The study, published in the journal Frontiers in Cellular Neuroscience, offers important insight into why myelin, the protective coating that surrounds nerve fibers, fails to regenerate in progressive MS, ultimately driving the disease’s advancement.

The Question

One of the mysteries of MS is why the nervous system does stops repairing itself in patients with progressive MS, particularly in primary-progressive MS, a continually worsening form of the disease.

The Research

Using state-of-the-art technology, researchers created patient-specific organoids — miniature, lab-grown models of the brain and spinal cord — to examine the biological mechanisms behind MS.

The organoids we created from people with PPMS showed low levels of a protein called p21, as well as dysregulated PAK1 and E2F1 gene expression. 

When p21 levels are low, the cells responsible for producing myelin (called oligodendrocytes) cannot function properly. Low p21 and dysregulated PAK1 and E2F1 negatively impact myelin repair mechanisms in the brain. 

The Impact

This discovery could pave the way for more targeted treatments that promote nerve repair and potentially slow MS progression. Most notably:

• It is the first paper to show that spinal cord organoids can be generated from patients with MS.
  • This is important, because it allow us to study human MS biology directly, and not rely solely on animal models.
• It shows that genetic factors (like p21 levels and dysregulated PAK1 and E2F1) partly predetermine whether people will develop relapsing-remitting MS or PPMS. 
• In the future, the study of organoid models like these will hopefully lead to individualized, patient-based treatments.

“Our research marks a significant step forward in understanding the cellular underpinnings of multiple sclerosis,” says Dr. Saud A. Sadiq.

 “By identifying how p21 dysregulation affects myelin repair and neuronal health, we open new possibilities for therapeutic interventions that could enhance neural repair and potentially improve patient outcomes.”

Read the full study here!