Revolutionary Pocket-Sized ALS Model: Experience Human-Like Breathing and Fluid Dynamics!

Scientists have developed a small, pocket-sized model to study amyotrophic lateral sclerosis (ALS), often called “Lou Gehrig’s disease.” This innovative “disease-on-a-chip” model, created using stem cells, could lead to new treatments for this progressive illness.

ALS affects motor neurons, the cells in the brain and spinal cord that control muscle movements. When these neurons weaken and die, signals to the muscles get disrupted, resulting in symptoms like muscle weakness, difficulty speaking, swallowing, and breathing.

A recent study published in Cell Stem Cell outlines the development of this new model for sporadic ALS, which accounts for up to 95% of cases and arises without any clear genetic cause. This model more accurately mimics the early stages of the disease compared to previous lab setups.

How It Works

Researchers started by taking blood cells from young ALS patients and healthy donors to create a “healthy” chip for comparison. These cells were transformed into induced pluripotent stem cells (iPSCs), capable of turning into any cell type. The scientists then developed spinal motor neurons from these stem cells.

In another part of the chip, they created cells that imitate the blood-brain barrier (BBB), which protects the brain from harmful substances. The spinal neurons and BBB cells were kept in separate chambers, but still interacted through a permeable membrane. This setup allowed a nutrient-rich fluid to flow continuously, helping the cells develop more fully.

“Dynamic flow of nutrients gives this model an edge,” said Clive Svendsen, a leading researcher in the study. It allows researchers to spot differences between ALS neurons and healthy ones more easily.

Dr. Kimberly Idoko, a neurologist and expert in the field, praised the new model for capturing early signs of ALS. “This chip improves neuron health and maturation, which is crucial for understanding disease progression,” she noted.

Key Findings

The researchers analyzed over 10,000 genes and discovered abnormal glutamate signaling in neurons on the ALS chip. Glutamate is a key messenger that helps neurons communicate. In the ALS neurons, glutamate activity was unusually high, while GABA (a calming neurotransmitter) activity was low. This imbalance could trigger neuron degeneration as ALS progresses.

Experts believe that heightened glutamate signaling may play a role in nerve damage seen in ALS. This aligns with existing theories and suggests that the chip could help identify how these changes happen before visible symptoms occur.

While this model has advantages, it also has limitations. For instance, it doesn’t include glial cells, which also play a role in ALS. Moreover, it does not replicate the late-stage degeneration that occurs in patients. Nonetheless, it may be valuable for early drug testing and understanding how potential treatments can cross the blood-brain barrier.

Future Directions

The researchers aim to keep the cells alive longer—up to 100 days—and include other cell types, like muscle cells, to better represent ALS progression. “Our goal is to create models that reflect more advanced stages of neuron death, providing deeper insights into the disease,” Svendsen added.

This new chip offers hope for better understanding ALS, facilitating early detection and potentially paving the way for new therapies.

For more on ALS research and treatment, visit Cleveland Clinic.

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