Recessive Neurodegenerative Disease

The Davidson laboratory studies inherited genetic diseases that cause central nervous system dysfunction and works to combat this with gene therapy targeted to the CNS. One form of Batten disease, a childhood onset neurodegerative disease, is due to a deficiency of a lysosomal protein, ceroid lipofuscinosis type III, or CLN3. We have showed that CLN3 is a lysosomal membrane protein and how mutations within CLN3 alter protein trafficking and function. Using in vitro transcription and translation experiments, we have begun to unravel how the protein orientates itself within the lysosomal membrane. Additional experiments are underway to test if CLN3 associates with other lysosomal or non-lysosomal proteins. We have ongoing studies aimed at determing CLN3 function within a cell. To approach these studies we generated a CLN3 life model for further disease study and to determine if gene transfer of CLN3 to the brain restores normal activity and is able to reverse disease phenotypes.  The ultimate goal is to understand how an absence of CLN3 leads to neurodegeneration, and to test if gene replacement rescues the disease phenotype.

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Recent Publications:

AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease.
Katz ML, Tecedor L, Chen Y, Williamson BG, Lysenko E, Wininger FA, Young WM, Johnson GC, Whiting RE, Coates JR, Davidson BL.
Sci Transl Med. 2015 Nov 11;7(313):313ra180 (Full text)

CLN3 deficient cells display defects in the ARF1-Cdc42 pathway and actin-dependent events.
Schultz ML, Tecedor L, Stein CS, Stamnes MA, Davidson BL.
PLoS One. 2014 May 2 (Abstract)

CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells.
Tecedor L, Stein CS, Schultz ML, Farwanah H, Sandhoff K, Davidson BL.
J Neurosci. 2013 Nov 13 (Abstract)

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