A recent study published in Cell Reports has identified a link between genetic variants in the ITSN1 gene and an increased risk of Parkinson’s disease. This research was conducted by an international team from Baylor College of Medicine, AstraZeneca, and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. The findings could lead to new treatments for slowing or preventing the progression of Parkinson’s disease.
Dr. Ryan S. Dhindsa, co-corresponding author and assistant professor at Baylor College of Medicine, stated, “Parkinson’s disease, the second most common neurodegenerative disorder, still has no cure. To tackle this unmet need, we analyzed genetic data from nearly 500,000 UK Biobank participants and discovered that individuals carrying rare ITSN1 variants that impair the gene’s normal function face up to a tenfold higher risk of developing Parkinson’s disease.”
The study's results were validated across three independent cohorts with over 8,000 cases and 400,000 controls. Carriers of ITSN1 variants also showed a trend toward earlier onset of the disease. Dhindsa noted the significant impact of ITSN1 compared to other genes like LRRK2 and GBA1.
Dhindsa further explained their focus on rare genetic mutations due to their large effects on disease risk and potential to reveal critical mechanisms. He said these discoveries enhance understanding of Parkinson's biology and identify new therapeutic targets.
ITSN1 is crucial for synaptic transmission in neurons—a process disrupted in Parkinson’s disease leading to symptoms such as impaired gait and balance. Dhindsa mentioned that reducing ITSN1 levels in fruit flies worsens Parkinson's-like features, with plans to extend research to stem cell and mouse models.
Previous studies have linked similar ITSN1 mutations to autism spectrum disorder (ASD), with emerging data suggesting an association between ASD and Parkinson’s disease. Dhindsa highlighted the need for future studies on these connections.
The study underscores ITSN1 as a promising therapeutic target and demonstrates the value of large-scale genetic sequencing in identifying rare mutations contributing to neurological disorders.
Contributors include Thomas P. Spargo, Chloe F. Sands, Isabella R. Juan among others from institutions such as Baylor College of Medicine, AstraZeneca, Rice University, and the University of Melbourne.
For more details on support sources for this work, refer to the publication.
