Dr. Dolores Pérez-Sala’s team - Research Update

Exciting research from Dr. Dolores Pérez-Sala’s team in Spain is shedding light on what happens inside brain cells in Alexander Disease (AxD). Their work points to a “vicious cycle” that could be key to future treatments!

What’s the Big Idea? A Problem that gets worse.

Think of your brain as a busy city. While neurons are known as messengers, other cells called astrocytes are the essential "housekeepers." They clean up, provide energy, and make sure everything runs smoothly. In AxD, the housekeepers are sick.

The Problem

A Faulty Building Block: Astrocytes are built with a protein called GFAP. In AxD, a tiny error (a mutation) in the instructions for GFAP means it gets assembled wrongly.

Oxidative Stress

Think of it as "Cellular Pollution". Healthy cells are powered by clean-running engines. When they get stressed, the engines become inefficient and produce harmful byproducts, like a factory that releases waste containing dangerous, reactive “pollutants” (oxidants), in amounts that the cell cannot clean up. These oxidants clog up the cell's machinery.

The Vicious Cycle of AxD

- Initial Problem: The faulty GFAP protein messes up the astrocyte's housekeeping duties. The cell's "power plants" (mitochondria) and "recycling centers" (lysosomes) can't work properly.

- Cell Gets Stressed: Because it can't function right, the astrocyte's engines sputter and produce way too much "cellular pollutants."

- Pollution Makes It Worse: This excess harmful pollution then damages the already faulty GFAP protein even more, making it clump together and become toxic.

- The Cycle Repeats: These new clumps make the astrocyte's housekeeping even worse, which creates even more pollution... and the cycle continues, amplifying the damage over time.

How Scientists Are Trying To Breaking the Cycle

Confirming if this cycle is a major driver in AxD

Testing if existing medicines can “clear the smoke” and help cells run cleaner

Searching for biomarkers—clues to track disease and if a treatment is working

By understanding this cycle, researchers can find the best points to intervene and help astrocytes get back to work.

A huge thank you to Dr. Pérez-Sala, her team, and collaborators—including the EU (Alexander consortium), Fundación “la Caixa” (Astromad consortium), Minoryx, and the Spanish Research Agency—for making this critical research possible.

Hope is growing. Each discovery brings us closer to treatments for Alexander Disease.