OMRF scientists uncover the source of a brain disorder similar to Parkinson’s disease

Oklahoma Medical Research Foundation scientists played a key role in a global effort to pinpoint the cause of a rare brain disorder similar to Parkinson’s disease.

An international team successfully traced the origin of the disorder to a specific genetic mutation found in 45 individuals from 28 families across multiple continents, including 11 people from six U.S. families.

Manifesting in early life, the unnamed disorder has been shown to cause significant motor and cognitive decline as affected individuals reach adulthood. Dr. Gaurav Varshney and his team, under the leadership of Dr. Sheng-Jia Lin at OMRF, played a crucial role in uncovering the cause using zebrafish with a genetic variant similar to that found in humans.

"This allows us to easily monitor their brain development and behavior," said Dr. Lin.

Zebrafish, known for their transparent larvae and external growth, proved instrumental in this research. Collaborating with Dr. Reza Maroofian in London, Dr. Varshney identified a mutation on the ACBD6 gene in three family members exhibiting similar neurological symptoms. Further investigation revealed the critical role of the ACBD6 gene in cellular and protein-modification processes, disruptions of which are linked to degenerative brain diseases.

The team's findings revealed that ACBD6 defects lead to a distinctive neurodevelopmental syndrome marked by complex cognitive and movement disorders. Clinical symptoms observed in affected individuals ranged from global developmental delay and expressive language impairment to movement disorders, facial dysmorphism and more.

Utilizing zebrafish and frog models, the study effectively mirrored the clinical phenotypes reported in patients. Dr. Varshney, the lead researcher, emphasized the importance of this breakthrough, noting that the knowledge gained from the zebrafish model could enhance understanding of disease progression. While the disorder in focus is rare, the researchers believe their findings may have relevance for more common neurodevelopmental diseases, including Parkinson's.

In the pursuit of practical applications, the international team now aims to explore ways to block the identified genetic variant as a potential strategy for preventing or treating the condition. This groundbreaking research opens new avenues for understanding genetic causes and pathways leading to neurodevelopmental diseases, offering hope for advancements in treatment and prevention.