Genetic discoveries could lead to sleep therapy for people with intellectual disabilities

The science is one step closer to developing targeted drug therapies that can reduce seizures, sleep disturbances and related symptoms common in people with intellectual disabilities.

Research by a team of neuroscientists at UNLV has shown the potential to focus on the root cause of a multitude of adverse symptoms associated with unique subtypes of neurodevelopmental disorders, work that could one day improve lives millions of people around the world.

The study, published on February 15 in the Nature newspaper Molecular psychiatrybuilds on previous research by UNLV neuroscientist Rochelle Hines and collaborators, who found that two key proteins – collybistin and the GABAA receptor α2 subunit – control brain cell firing and contribute to seizures, learning and memory disorders, sleep disturbances and other symptoms commonly associated with various forms of intellectual disability, including Down syndrome, autism and ADHD.

The team’s most recent findings revealed that mutations in ARHGEF9 – the gene that codes for collybistin – lead to intellectual disability due to impaired α2 subunit function. The team further showed that α2 is a central hub for many adverse neurological symptoms characteristic of several subtypes of intellectual disability.

“Seizures and sleep deficits are two of the most common and disruptive symptoms in children with neurodevelopmental disorders, and sleep deficits in particular are not well treated and can impact the whole family. “said Hines, who partnered with UNLV faculty and undergraduate and graduate students. student researchers, as well as scientists from Tufts University and Boston Children’s Hospital. “This research gives new hope to patients that we can now develop drug therapies and provide more precise interventions.”

In addition to patients with neurodevelopmental disorders, the researchers said their study has the potential to improve the quality of life more broadly for people struggling with sleep disorders, epilepsy, anxiety, hyperactivity and other neurological abnormalities.

Take away food

  • Intellectual disability is a common neurodevelopmental disorder that can result from genetic mutations. People with these disorders – Down syndrome and autism being the most common – frequently report related symptoms such as seizures, learning and memory difficulties and disturbed sleep-wake cycles.
  • By manipulating the interaction between two key brain proteins, scientists discovered that one of them, called the α2 subunit, plays a more critical role in intellectual disability and related symptoms than researchers thought. previously.
  • Knowing which functional interaction is responsible for triggering the adverse effects caused by ARHGEF9 gene mutations will help researchers develop precise drug interventions, resulting in improved patient care.
  • Further research is underway, with the hope that the work may one day move into clinical trials.

Reference: Hines DJ, Contreras A, Garcia B, et al. The human intellectual disability syndrome ARHGEF9 is phenocopied by a mutation that disrupts the binding of collybistin to the α2 subunit of the GABAA receptor. Mol Psychiatry. 2022:1-13. doi: 10.1038/s41380-022-01468-z

This article was republished from the following materials. Note: Material may have been edited for length and content. For more information, please contact the quoted source.

Norma A. Roth