Targeting aberrant glycogen metabolism in CLN3 disease

CLN3 disease is a devastating pediatric neurodegenerative disease without a cure. Based on the PI (Wang)’s previous work and preliminary data, loss of CLN3, the gene mutated in the disease led to extensive metabolic impairment. Specifically, we were the first to report striking glycogen accumulation in CLN3 deficient cells. Our RNA-Seq and Stable Isotope Resolved Metabolomics (SIRM) data further reveal aberrant glycogen metabolism in CLN3-deficient cells. Intrigued by the Co-I (Gentry)’s recent discovery of aberrant glycogen metabolism in causing neurodegeneration in Lafora disease, in this proposed pilot project, the PI and Co-I will joint force to address the molecular mechanism of how aberrant glycogen metabolism may lead to neurodegeneration and neurological deficits in CLN3 disease, and to develop novel glycogen metabolism-relevant disease biomarkers and a novel therapy targeting aberrant glycogen metabolism.