Tiny Worms May Unlock New Treatments for Rare Childhood Disorder

Rare Daily Staff

Researchers at Brown University have developed genetically engineered versions of C. elegans—tiny worms commonly used in research — to model alternating hemiplegia of childhood (AHC), a rare neurological condition that causes episodes of paralysis, seizures, and other serious symptoms.

The work, published in the journal Disease Models & Mechanisms, offers a faster and more cost-effective way to study the disease and test potential therapies. Because humans and C. elegans share many genes, including those linked to AHC, the worms can mimic key aspects of the condition.

“These animals are incredibly useful for rapidly screening drugs,” said Anne Hart, a professor at Brown University’s Carney Institute for Brain Science. “Their simplicity allows us to test many compounds quickly and identify which ones might have the greatest impact.”

AHC is caused by mutations in a gene called ATP1A3, which produces a protein essential for normal nerve and muscle function. Children with the condition can experience episodes of paralysis lasting anywhere from minutes to days, along with muscle spasms, developmental challenges, and disruptions to basic bodily functions. The disorder has no cure and very limited treatment options.

One of the challenges in treating AHC is that symptoms vary widely from patient to patient. The researchers addressed this by creating multiple worm models, each carrying different disease-related mutations. The results showed that each mutation disrupted nerve and muscle activity in distinct ways — mirroring the variability seen in children with AHC.

“Each model shows slightly different problems in behavior and neurological function,” said Brown doctoral student Diana Wall, who led the study. “That reflects what we see in patients, where different mutations lead to different symptoms.”

Compared with existing models — such as mice or lab-grown human cells — the worm system is easier to scale and includes some of the most common AHC mutations. This makes it especially promising for drug discovery efforts.

Researchers say the model could allow them to screen thousands of potential treatments across several common variants of the disease, dramatically accelerating progress in a field that has long lacked effective options.

Photo of C. elegans by Diana Wall/Brown University