Rare Disease, Real Results: The Team That’s Exploding Research for a Rare Brain Disorder
By Mackenzie Smith, C2ST Intern, Loyola University
Imagine your child is sick, and no amount of doctor visits provides a satisfying answer as to what they are facing. Before 2016, this was the case for families affected by a rare disease known as Okur-Chung neurodevelopmental syndrome, or OCNDS. This all changed when researchers discovered mutations in the gene “CSNK2A1.” These mutations cause what is now known as OCNDS. I sat down with the Chief Scientific Officer of the CSNK2A1 foundation, Dr. Gabrielle Rushing, to reflect on this earth-shattering finding now that nearly a decade has passed. Together we discussed the important question: When a rare mutation is found, what are the next steps to make meaningful changes in the lives of patients?
What is OCNDS?
OCNDS is a developmental disorder that heavily impacts the brain. Therefore, patients have intellectual disability, language delays, and may even be nonverbal. About a third also experience seizures. Aside from neurological challenges, patients could be short in stature and have muscle weakness, which may be linked to GI tract issues like constipation. Dr. Rushing shared that one of the top impactful issues that caregivers are concerned with is poor sleep quality associated with the disease.
Since 2016, Almost 300 patients worldwide have been diagnosed. However, Dr. Rushing says it’s estimated that 1 in 100,000 people have this disorder. She expects that there are patients not being recognized due to issues with access to diagnostic tools or low awareness of symptoms.
What has discovering the mutation meant for patients and families?
Before 2016, these patients’ charts included vague indications that they had autism, developmental delay, or motor issues. Now, they can receive a more personalized diagnosis that accounts for their unique symptoms. On top of that, identifying the CSNK2A1 mutation paved the way for establishing a foundation.
Dr. Rushing lit up when telling this story and sharing everything she and the team have accomplished. She explained that Jennifer Sills started the CSNK2A1 foundation in 2018 because her daughter Jules was the 6th person in the world to be diagnosed with OCNDS.
Over the past few years this foundation has built up a wealth of resources Sills knows will be important for families. At the time of her daughter’s diagnosis, Sills was simply handed the original research paper describing the disease. The paper was full of jargon and she struggled to understand the dense scientific language. To alleviate this issue for future patients and carers, the “research explained” page on the foundation website was created to put complex research into language that’s easier to understand. They have also established a conference that connects families to researchers, ensuring that they work together to decide the goals for OCNDS research.
What has this discovery meant for science?
Connecting CSNK2A1 mutations to neurodevelopmental delays has naturally transformed the landscape of scientific research on this gene. Previously, overactivation of this gene had been associated with cancers. Now, there is growing interest in seeing how it causes developmental issues when it is less active.
The CSNK2A1 foundation has outlined a research strategy to answer pressing questions about this mutation. Dr. Rushing works closely with those at the cutting edge of this research and was excited to praise the latest achievements in the field. For instance, two projects were recently funded to examine nasal swabs or cells taken from patients to understand how they differ from those without the disorder. These differences can give scientists ideas about what medications could be used to help those with OCNDS.
What’s on the horizon?
Speaking on her position as Chief Scientific Officer, Dr. Rushing says, “It’s one of those jobs that relights a fire under you.” The passion behind those affected by or studying the disease is apparent. This dedicated team, which Dr. Rushing calls “collaborative,” is pushing for important milestones in raising awareness and accelerating research. For example, they are working to get CSNK2A1 included in genetic testing panels looking for autism or epilepsy genes to help make sure every patient can put a name to what they are facing. Soon, they plan to reach out to pharmaceutical companies interested in similar diseases to get them invested in developing OCNDS treatments.
What has been accomplished in the eight years since the discovery of the CSNK2A1 mutation is staggering. This work is critical to better understanding the disease and developing targeted treatments. To learn more, visit the CSNK2A1 foundation website, read the report by the National Organization on Rare Diseases, or check out a publication by Dr. Okur and Dr. Chung themselves.
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