Research Project Director, Kuan Wang, Ph.D., Research Project Co-Director, John Foxe, Ph.D., Project Co-Investigator Heather Adams, Ph.D., Project Co-Investigator, Edmund Lalor, Ph.D., Study Coordinator, Tufikameni Brima, Ph.D.,
The Neuronal Ceroid Lipofuscinoses (NCL) are a group of neurodevelopmental diseases categorized as autosomal recessive lysosomal storage disorders, and are characterized by intracellular accumulation of ceroid lipofuscin. Clinical features include vision loss, seizures, motor decline, and progressive dementia. CLN3 disease (classic Juvenile Neuronal Ceroid Lipofuscinosis, JNCL) is one of the most common types of NCL, and results from mutations in the CLN3 gene on chromosome 16. Individuals with CLN3 disease experience progressive cognitive decline over late childhood and early adolescence. The precise neuropathologic bases of this decline are not yet well understood and objective neurologic biomarkers (neuromarkers) of disease progression are not currently available. There is a critical need for such markers to provide more sensitive outcome measures against which to test the effectiveness of therapeutic approaches currently in development, and to aide in the objective staging of disease progression.
The project takes a translational, three-pronged approach to development of reliable neuromarkers for persons with Batten disease, and in parallel, extends two murine models of CLN3 disease to enhance efforts to understand the underlying cellular mechanisms of the disease. Aim 1 of this project builds on our extensive pilot work in which we identified disease-specific patterns of change in the auditory evoked potentials (AEPs) of children with neuronal ceroid lipofuscinosis (NCLs). In Aim 2, we re-deploy EEG measures of auditory perception that were used in our CLN3 human participants (Aim 1) in a pair of murine models of CLN3 disease. In Aim 3, we focus on the cellular mechanisms that lead to neuronal loss with particular attention paid to auditory processing networks. This work is built on the foundational work of our UR Batten’s Center (URBC), the home of the nation’s largest CLN3 disease patient registry and natural history study, which positions the UR-IDDRC team to deploy its biomarkers into clinical trials as the proposed research project herein yields actionable results.