OBJECTIVES/SPECIFIC AIMS: We present an alternative strategy to retain NTFs at an injected CNS tissue site by endowing them with binding affinity for carbohydrates that are abundant on the cell surface and within extracellular matrices. METHODS/STUDY POPULATION: We are creating recombinant fusions in which glial cell-derived neurotrophic factor (GDNF) is linked to galectin-3 (G3), a human protein that binds to extracellular beta-galactoside glycans and glycosaminoglycans. GDNF-G3 fusion proteins will circumvent major therapeutic shortcomings of early GDNF human trials by anchoring GDNF to the midbrain in a preclinical animal model of PD over a therapeutically-relevant timescale in order to achieve DA neuron rescue. Further, in PD patients, we have detected significantly dysregulated dopamine signaling in peripheral, blood-derived monocytes, suggesting a systemic dopamine signaling change in PD. RESULTS/ANTICIPATED RESULTS: Based on results from published human NTF administration trials, we anticipate that a successful intervention using GDNF-G3 will result in rescue or delayed degeneration of midbrain dopaminergic neurons in a murine PD model. Outcome measures include behavioral PD phenotype testing via rotarod and pole descent compared to non-parkinsonian control animals, as well as corroborating immunohistological evidence from immunohistochemical examination of post-mortem brain tissue from the same animals to examine degree of degeneration. DISCUSSION/SIGNIFICANCE OF IMPACT: Current treatments for PD, whether pharmacological or surgical, center on alleviating movement symptoms that impair daily function - in other words, largely palliative care. Little has been accomplished by way of rescue of dopaminergic neurons or slowing disease progression using standard-of-care therapy. If successful, GDNF-G3 constructs administered intracranially at the site of degeneration would represent a milestone on the path to treating the basic pathology associated with PD, while addressing major shortcomings in earlier NTF-delivery attempts, namely NTF diffusion away from target site.