Date of Award
Master of Science
Dr. Tony Rupar
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a mutation in the enzyme, arylsulfatase A (ASA) and is characterized by progressive and fatal demyelination in the central and peripheral nervous systems. To date, no effective treatment exists and development is hampered by the blood-brain barrier (BBB). I have successfully generated fusion proteins using an ApoE fragment as a molecular Trojan horse fused to the full-length human ASA. These proteins were expressed in eukaryotic cells transduced with lentiviral expression vectors and have been assessed for in vitro enzymatic activity and kinetic properties. Although preliminary studies show that these constructs did not cross an in vitro BBB model under these experimental conditions, there is evidence to suggest that the ApoE fragment facilitates the uptake of fusion proteins into the endothelial cells of the BBB. Recommendations for further study are encouraged to reach the goal to find treatment for MLD
Baer, Katherine Marie, "MOLECULAR TROJAN HORSES IN THE TREATMENT OF METACHROMATIC LEUKODYSTROPHY" (2011). Digitized Theses. 3441.