Katie Pulsipher: “Current Landscape of Enzyme Replacement Therapy and Considerations for GAMT Deficiency”
ABSTRACT
This poster will provide an overview of the current landscape in approved enzyme replacement therapies and considerations for the development of an enzyme replacement therapy (ERT) for GAMT deficiency. Enzyme replacement therapy provides functioning recombinant enzymes to patients with an enzyme-based disorder. ERTs are typically administered at least once every two weeks, either by intravenous infusion or subcutaneous or intramuscular injection. Most currently available ERTs are approved for lysosomal disorders, due to the difficulty of endosomal escape once an enzyme is introduced into the bloodstream. This presents a challenge for GAMT, which needs to localize to the cytosol to be effective in creatine synthesis. Considerations for how to deliver active GAMT to its proper intracellular location will be important in the development of an effective ERT for GAMT deficiency. Other factors to consider include potential enzyme modifications to enable manufacturing feasibility, ensure enzymatic stability, and explore passage through the blood-brain barrier.