Understanding ALS: a new research project with organoids and molecular mapping

The Challenge:

Amyotrophic Lateral Sclerosis (ALS) is a devastating disease that progressively destroys the nerve cells responsible for controlling movement. People with ALS gradually lose the ability to move, speak, eat, and eventually breathe. Despite years of research, we still do not have treatments capable of stopping or reversing ALS. A major obstacle is that we have not yet fully understood how the disease begins and progresses.

Our Innovative Approach:

We plan to create 3D versions of brain, spinal cord, and muscle tissue—called “organoids”—grown in the laboratory from cells donated by ALS patients. We will connect these mini-organs to each other to mimic their interactions in the body, creating a living model of the connection between the nervous system and muscles that can be studied in the lab.

What We Will Do:

• Generate organoids: we will culture brain, spinal cord, and muscle organoids from cells donated by ALS patients and assemble them together to create a functional 3D system.
• Observe them: we will measure electrical activity and muscle contractions to ensure that the organoids behave like real tissues.
• Create molecular maps: using cutting-edge technology called MERFISH, we will generate detailed maps showing exactly which genes are active in which cells of our 3D system. MERFISH can simultaneously track hundreds to thousands of different RNA types within a single cell, producing a precise map that displays both the amount and exact location of each RNA type, giving a complete view of which genes are active in specific parts of the cell.
• Track changes over time: by examining these systems at 3, 6, and 9 months, we will observe how ALS develops and progresses.
• Test potential treatments: once we identify the molecules that change first in ALS, we will target them with potential therapies in our 3D system to see if we can stop or slow the progression of the disease.

Why it matters:

By understanding exactly where and how ALS begins, we can::

Develop treatments that target the disease at its origin, not just its symptoms

Test potential drugs on human tissue before clinical trials

Possibly identify early signals of ALS before symptoms appear

Apply similar approaches to study other neurological diseases

This project combines the latest advances in the in vitro study of human tissues with powerful molecular mapping techniques to create a view of ALS that was previously impossible. By observing disease development in these interconnected organoids, our long-term goal is to identify new pathways that lead to the development of effective treatments for people living with ALS.

Budget:

To get started, the project requires a budget of €70,000.