{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/18441"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/18441","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"MOLECULAR TROJAN HORSES IN THE TREATMENT OF METACHROMATIC LEUKODYSTROPHY","abstract":"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","abstract_html":"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","abstract_has_math":false,"creators":["Baer, Katherine Marie"],"institution":null,"degree_name":"M Sc","degree_level":null,"degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Rupar, Tony"],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-01","date_published":"2011-01-01","updated_at":"2026-07-27T21:56:09Z","subjects":["MLD","ASA","molecular Trojan horse","ApoE","fusion protein","blood brain barrier"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/18441","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Rupar, Tony"]},{"key":"dc:creator","label":"Author","values":["Baer, Katherine Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-25T18:50:19Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-06-25T18:50:19Z"]},{"key":"dc:date.issued","label":"Date","values":["2011-01-01"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["MLD","ASA","molecular Trojan horse","ApoE","fusion protein","blood brain barrier"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/18441"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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"]},{"key":"dc:title","label":"Title","values":["MOLECULAR TROJAN HORSES IN THE TREATMENT OF METACHROMATIC LEUKODYSTROPHY"]}]}],"canonical_facts":{"dc:contributor.advisor":["Rupar, Tony"],"dc:creator":["Baer, Katherine Marie"],"dc:date.accessioned":["2025-06-25T18:50:19Z"],"dc:date.available":["2025-06-25T18:50:19Z"],"dc:date.issued":["2011-01-01"],"dc:description.abstract":["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"],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/18441"],"dc:subject":["MLD","ASA","molecular Trojan horse","ApoE","fusion protein","blood brain barrier"],"dc:title":["MOLECULAR TROJAN HORSES IN THE TREATMENT OF METACHROMATIC LEUKODYSTROPHY"],"dc:type":["thesis"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:09Z"}