A new research center has launched with the aim of developing gene therapies for rare genetic brain disorders, beginning with conditions that cause seizures in children. The initiative, supported by a $34.5 million contract from the Advanced Research Projects Agency for Health (ARPA-H), complements ongoing efforts to address neurological diseases through gene editing technologies.
The center’s work is initially focused on alternating hemiplegia of childhood (AHC) and Dravet syndrome, two rare and severe neurological disorders that often manifest early in life. AHC affects approximately 400 children in the United States and involves episodes of paralysis and seizure-like symptoms. Dravet syndrome, a genetic form of severe epilepsy, occurs in about one in 15,700 births and carries a high mortality rate, with 20% of affected individuals dying before age 18.
Patients and families affected by these conditions have long faced challenges due to the scarcity of treatments and the difficulty of attracting commercial investment. Annabel Frost, a 10-year-old with AHC, and Elliot Meskis, a 26-year-old with Dravet syndrome, represent individuals whose families have been actively engaged in raising awareness and funding to support research. Annabel’s parents, Simon Frost and Nina English Frost, founded a nonprofit that has raised over $4 million in eight years to advance gene therapy research tailored for their daughter’s disease.
The scientific effort is led by Dr. David Liu of the Broad Institute, who has pioneered gene editing approaches capable of targeting mutations in brain cells. While previous studies have demonstrated success in mouse models, translating these therapies to humans presents significant challenges, particularly in delivering gene editors across the blood-brain barrier—a protective membrane that prevents many substances from entering the brain.
Researchers have developed a method to circumvent this obstacle by engineering viruses that can cross the blood-brain barrier via a carrier protein normally responsible for transporting iron into the brain. The viruses carry gene-editing instructions that, once inside brain cells, can correct disease-causing mutations by rewriting defective genes into their healthy versions.
Treatment under this new approach would begin with intravenous injections of the engineered virus, potentially allowing for delivery to brain cells without invasive procedures. Although initial trials will focus on children most severely affected by AHC and Dravet syndrome, the goal is to establish a platform applicable to a broader range of genetic brain diseases, including adult-onset conditions like Huntington’s disease.
Experts acknowledge that developing gene therapies for rare neurological diseases will be a lengthy and difficult process. However, the center’s emphasis on sharing its research openly sets it apart from traditional for-profit models, potentially accelerating progress across the field. Dr. Mark Kay of Stanford University, who is not affiliated with the center, praised the initiative’s commitment to transparency, highlighting its potential to foster wider adoption by other researchers.
Clinicians involved express a strong sense of urgency. “My patients don’t have time to wait,” said Dr. Chung, a researcher on the team. The center hopes its efforts will lay the groundwork for effective treatments and ultimately improve the lives of millions affected by rare genetic brain disorders worldwide.