Research from the University of Rochester has uncovered significant insights into how sex and age affect the progression of Batten disease, particularly the CLN3 variant. This rare inherited disorder, which impacts brain development and function, typically manifests symptoms between the ages of four and seven, leading to vision loss, cognitive impairment, movement issues, seizures, and speech difficulties. While males and females are both affected, the study highlights marked differences in disease onset and progression.
The paper, published in the Journal of Neurodevelopmental Disorders on March 15, 2025, reveals that male patients often experience earlier symptoms that may improve with age, whereas female patients tend to show a later onset and a more rapid progression of the disease. This critical finding underscores the need for tailored treatment approaches based on sex-specific responses.
Groundbreaking Methodology
Researchers employed electroencephalography (EEG) to noninvasively measure brain electrical activity and assess auditory responses in both male and female mouse models of CLN3 disease. The study’s first author, Yanya Ding, Ph.D., noted the challenges of tracking disease progression due to the early decline in vision and cognition. She stated, “Being able to successfully track brain functions in mice gives us a model that could transform how we study possible treatments and therapeutics for this devastating disease.”
The findings revealed that male mice exhibited early auditory deficits that improved with age, while female mice faced ongoing challenges. This data suggests that both sex and age significantly influence the neurophysiological impact of Batten disease, presenting a new framework for understanding its progression.
Implications for Future Treatments
The co-senior author of the study, John Foxe, Ph.D., who leads the Fredrick J. and Marion A. Schindler Cognitive Neurophysiology Lab at the University of Rochester, previously identified key biomarkers in human CLN3 patients. These biomarkers facilitated the current mouse study, establishing a connection between human and animal research that could enhance treatment strategies.
Another co-senior author, Kuan Hong Wang, Ph.D., emphasized the importance of utilizing EEG-based methods for monitoring disease progression. He stated, “These findings highlight the importance of tracking brain function over time and support the use of this EEG-based method as a valuable tool for monitoring disease progression and testing new treatments.”
The University of Rochester is recognized as an Intellectual and Developmental Research Center (IDDRC), focusing on discovering neuromarkers associated with Batten disease. With several potential gene therapies in advanced stages of development, the translational mouse model provides an innovative platform for evaluating the effectiveness of these experimental treatments.
The research team also included co-first author Jingyu Feng, along with colleagues Viollandi Prifti, Grace Rico, Alexander Solorzano, Hayley Chang, and Edward Freedman, Ph.D., from the University of Rochester Medical Center.
As understanding of Batten disease deepens, this research paves the way for more personalized therapies, potentially improving outcomes for those affected by this challenging condition. The study’s insights may prove invaluable in guiding future interventions and treatment strategies tailored to individual patient profiles.
