2013 Research

Grant Amount: $18,000

Grant Date: July 2013

Research Proposal: Evaluate mutations in the GNPTAB gene that give rise to mucolipidosis II (I-­‐cell disease) and mucolipidosis IIIα/β(Pseudo-­‐Hurler Polydystrophy). There are 2 specific aims of this project; (1) Attempt to rescue the misfolding of the 9 mutant enzymes using pharmacological agents; (2) Define the basis for the lack of activity toward lysosomal acid hydrolases in the mutants that fold properly and localize correctly in the Golgi.

Status: Research completed. Please see below for results.

Result: Drs. Steet and Kornfeld have provided a midterm update on their YGF-funded research project. They are pleased to report the identification of a new region within the GlcNAc-1-phosphotransferase enzyme that is responsible for the specific recognition of lysosomal enzymes. This finding is significant since it helps explain why certain ML mutations contribute to ML-II vs ML-III, and deepens our understanding of the genetic basis for this disease. The researchers hope to utilize this information to develop therapies for ML disease that can be tailored to specific mutations found in patients.