Therapy-oriented research of rare diseases of central nervous system.

Our research is focused on pre-clinical studies and biomarker discovery for rare pediatric neurologic diseases with high unmet need to enable further development of therapies. Our therapeutic strategies have been focused on use of adeno-associated viral vectors for optimized transduction and transgene delivery to central nervous system, including brain, retina, and optic nerve. Our second line of research is focused on understanding the role of lysosomal and autophagy pathways in brain development and disease and harnessing lysosomal signaling for treatment of central nervous system.

1. Therapy development for Mucolipidosis IV (MLIV). We have created disease-relevant cell and mouse models of mucolipidosis IV and described pathophysiology of MLIV in the mouse brain and eye. We have designed and performed efficacy testing of the AAV-based gene therapy approach in MLIV mice. Our strategy is focused on optimized delivery of human MCOLN1 transgene to combat CNS impairment and vision loss in MLIV.
2. Biomarker discovery for Mucolipidosis IV. Using MLIV mouse and human patient sample sets, we perform biomarker discovery for future clinical trials using lipidomics and proteomics techniques. Guided by clinical observations in MLIV patients, we also conduct a study of brain neurotransmitter metabolites as potential biomarkers of MLIV.
3. Gene therapy approach to treat beta-propeller protein associated neurodegeneration (BPAN).
   We test efficacy of brain-targeted AAV-mediated gene-replacement of WDR45 for treatment of BPAN.
4. MCOLN1 gene therapies for lysosomal and autophagy diseases. MCOLN1 gene encodes lysosomal channel TRPML1 which is a master regulator of lysosomal function and autophagy. Here we investigate whether AAV-mediated overexpression of MCOLN1 gene may provide therapeutic benefit in diseases with impaired lysosomal and autophagy pathways.