Date of Award
Bachelor of Science
Lysosomal storage diseases (LSDs) are a set of inborn errors of metabolism characterized by deficiencies in acid hydrolases that lead to substrate accumulation in cells and decreased or absent formation of downstream products. Substrate buildup can result in a wide range of symptoms affecting multiple peripheral organ systems and the central nervous system. Disease onset is commonly observed in infancy or childhood, but adult-onset forms also occur. Current treatments include enzyme replacement therapy and substrate reduction therapy, which are effective in the short term, but gene therapies are emerging as a potential long-term and efficacious treatment option. Delivery of gene therapy is accomplished by using adeno-associated viruses, specifically serotypes 9 and 10, and lentiviruses due to their ability to reach the central nervous system. Modifications to these vectors and intracerebroventricular, intrathecal, or intravenous delivery can maximize transgene expression in affected tissues. Results from animal studies show the promise of these therapies to treat Krabbe, Fabry, and Gaucher disease. Early treatment administration showed the best outcomes for increasing life span and clearance of accumulated substrates. Combination therapy shows promising results when gene therapies were given in addition to bone marrow transplants in animal models. Next-generation sequencing technology allows for the reliable identification of pathogenic variants that can lead to LSDs and successful gene therapy experiments in animal models reveal the potential for clinical application.
Borgida, Jake, "Lysosomal Storage Diseases: How Gene-Targeted Therapies are Changing What is Treatable". Senior Theses, Trinity College, Hartford, CT 2023.
Trinity College Digital Repository, https://digitalrepository.trincoll.edu/theses/1028