Section 1: Breakthrough in Understanding Genetic Protein Overproduction
Researchers at Northwestern Medicine and the Broad Institute of MIT and Harvard have made a groundbreaking discovery in understanding a rare neurodevelopmental disorder caused by protein overproduction. The disorder, resulting from the chromodomain helicase DNA binding (CHD2) gene, leads to severe developmental delays, leaving patients wheelchair-bound, non-verbal, and with profound intellectual disabilities. The new study, set to be published in the New England Journal of Medicine, identifies a key player in controlling protein production—an RNA called CHASERR (CHD2 adjacent, suppressive regulatory RNA).
CHASERR, a long non-coding RNA, acts as a brake to regulate how much CHD2 protein is produced. In patients with this rare disorder, the deletion of CHASERR removes this brake, causing CHD2 protein levels to surge. This overproduction of protein is linked to the severe neurodevelopmental effects seen in patients. The discovery of this RNA mechanism opens the door to new treatments that could target CHASERR to manage protein levels and alleviate symptoms in patients with conditions such as epilepsy and autism.
Section 2: Unveiling the Role of Long Non-Coding RNAs
Unlike most RNAs, which create proteins, long non-coding RNAs like CHASERR do not directly produce proteins but play a crucial role in regulating gene activity. This discovery sheds light on the largely unexplored “Wild West” of the human genome, where 99% of genetic material remains understudied. Dr. Gemma Carvill, the study’s lead author, noted that this is the first time researchers have linked a CHASERR deletion to protein overproduction in humans, building on earlier studies in mice by Dr. Igor Ulitsky at the Weizmann Institute.
The team analyzed three patients with excessive CHD2 protein production and found that all had a deletion of CHASERR RNA. This deletion caused the CHD2 gene to go into overdrive, resulting in the neurodevelopmental disorder. Moving forward, researchers hope to manipulate CHASERR to control protein production, paving the way for potential treatments that address the root cause of the disorder rather than just managing its symptoms.
Section 3: Impact on Future Genetic Research and Treatments
The study highlights the importance of investigating the full human genome, especially non-coding regions that control gene expression. Dr. Carvill emphasized that while current genetic testing focuses on just 1% of the genome that codes for proteins, the other 99%—including long non-coding RNAs—holds significant potential for understanding and treating genetic disorders. This discovery underscores the need for more comprehensive genome testing to identify hidden genetic variants that could be causing rare diseases.
One of the patients involved in the study, 8-year-old Emma Broadbent, provided a personal connection to the research. Emma’s father, Brian, searched for answers after learning about her deletion of CHASERR and connected with scientists like Dr. Carvill to help push the research forward. Now, this study represents a significant step toward finding answers for other families affected by similar disorders.
Looking ahead, the researchers hope to develop gene-targeting therapies that address the genetic changes causing disorders like epilepsy, which currently affects many patients who do not respond to conventional antiseizure medications. By targeting non-coding regions like CHASERR, scientists may be able to develop more precise treatments that address the root cause of these conditions, offering new hope for patients and families.