Israeli scientists have created the first successful mouse model of a rare and often fatal genetic disorder, opening a door to personalized therapies, according to the Press Service of Israel (TPS-IL).
The condition, simply known as the GRIN2D mutation, is a mutation of the GRIN2D gene that causes severe epilepsy, developmental delays, and, in many cases, early death. It affects about 40 people worldwide, mostly children. The new model allows scientists to study the disease closely and test treatments.
The research was led by Professors Moran Rubinstein and Karen Avraham from the Tel Aviv University’s Gray Faculty of Medical and Health Sciences. They were approached by the parents of Adam, an Israeli boy now eight years old, who was diagnosed with the GRIN2D mutation at age two. “Adam is one of a very small number of children in the world with this disease,” said Avraham. “His case gave us the push to try and find a treatment.”
Adam’s mother, Eden Maimon Banet, said, “We met an amazing team that took on this mission with real heart. Their personal connection to Adam gave us hope. And now, we’re finally seeing results.”
The first attempt to create a mouse model failed because the mice died too soon. But the team found a way to engineer mice that carried the same mutation without early symptoms, allowing them to breed mice that showed clear signs of the disease — just like in human patients. The team’s study was published in the peer-reviewed journal, Brain.
Studying these mice gave the scientists valuable new insights. They found that seizures and movement problems began early in life, while learning difficulties appeared later and worsened over time. Most affected mice died young, often from severe seizures.
“Until now, no one really knew how the disease progressed,” said Rubinstein. “The model gave us a clear picture of what happens over time.”
Brain scans revealed a major discovery: in both children and the mice, brain activity was constantly abnormal—not just during seizures, as seen in most epilepsies. “That pattern matched exactly between humans and mice,” said Rubinstein. “It confirmed that our model works.”
The team also tested drugs. Ketamine, once thought to help, actually made things worse. But memantine and phenytoin showed some positive effects, improving brain activity and reducing symptoms.
Prof. Moran Hausman-Kedem of Dana-Dwek Children’s Hospital in Tel Aviv said, “This model is a huge step forward. It lets us test treatments safely and understand what might help before trying it in children.”
The team is now testing more drugs and genetic therapies. Early results show improvements in thinking, movement, and lifespan in the mice. “We hope this brings new options for Adam and other children like him,” said Rubinstein.
Because GRIN2D is part of a broader family of GRIN-related disorders, this model may also inform treatment and research for similar neurological conditions, such as other GRIN mutations or early-onset epilepsies involving NMDA receptor dysfunction.
