Breakthrough Model for Rare Genetic Disease Unveiled by Tel Aviv University Researchers: What It Means for Patients

Researchers at Tel Aviv University have made a major breakthrough in treating a rare genetic disorder linked to the GRIN2D gene. They have developed a mouse model that mimics the disease, offering a valuable tool for studying its progression and testing therapies. This work could change the lives of children affected by this condition.

Led by Professors Moran Rubinstein and Karen Avraham, the study was published in the journal Brain and involved collaboration with scientists from Columbia University and the Dana-Dwek Children’s Hospital in Tel Aviv. This research was inspired by Adam, an eight-year-old from Israel, one of only 40 known cases worldwide. Adam suffers from a mutation in the GRIN2D gene, which leads to developmental epilepsy and severe delays in motor skills and cognition.

Adam’s mother, Eden Maimon Banet, shared how dedicated the research team is. She said, “We met a wonderful team focused on finding a treatment for our son. We are beginning to see hope.”

To create the mouse model, researchers replicated Adam’s genetic mutation. Initially, the mice didn’t survive long after birth, making research difficult. However, the team discovered a way to breed mice with both affected and unaffected offspring, which allowed them to study the disease effectively. They found that neurological symptoms appeared early, while cognitive impairments developed later. Sadly, most affected mice lived only a few weeks, though some lasted up to three months.

Professor Rubinstein explained, “We were able to see symptoms develop at different stages. Infants showed neurological issues, while cognitive problems became clear later.” They observed significant changes in the brains of these mice, particularly in the cerebellum. EEG tests revealed abnormal activity patterns consistent with what’s seen in human patients. “We found the same brain abnormalities in both mice and people, affirming the model’s relevance,” he noted.

In addition to developing the model, the team tested existing drugs. Ketamine, previously thought to help, worsened seizures. But memantine, which is already used for conditions related to GRIN2D, showed some improvement. Another common anti-seizure medication, phenytoin, also helped.

Professor Moran Hausman-Kedem, a pediatric neurologist involved in the project, emphasized the importance of this model. “For rare diseases, patient populations are often too small for large-scale trials. Mouse models are vital for guiding treatment decisions by providing insights into the safety and effectiveness of therapies.”

The team continues its work, investigating new drug and gene therapy options. Early results look positive, showing improvements in cognition, motor skills, and slight increases in lifespan for the mice.

“Our research has deepened our understanding of the disease and the efficacy of existing medications,” Rubinstein said. “We’re hopeful our ongoing work can bring real relief to families dealing with this debilitating disorder and others like it.”

Supported by a variety of foundations, including the US-Israel Binational Science Foundation and the GRIN2D Project Foundation, this research shines a light on the potential for new treatments in the field of rare genetic disorders.

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