GLA-T Gene Therapy
GLA-T Gene Therapy uses genetically-modified T Cells that have been rendered non-activated through exposure to rapamycin (T-rapa). The T-rapa cells are modified by lentivector to express a therapeutic transgene utilizing the “TRAM” micropharmacy technology (PMID 35298086 ). In the context of Fabry disease, the missing gene is GLA, which encodes for the alpha-galalactosidase A (a-gal A) enzyme.
The procedure involves harvesting the patient’s lymphocytes by apheresis.
T-cell populations are isolated and treated for rapamycin adjustment to make T-rapa cells.
T-rapa cells are transduced with lentivector to create a modified, attenuated T-cell (the TRAMs).
The TRAM population is transfused back into the patient where they systemically spread and perdure.
In the GLA-H procedure, the modified T-cells offer multiple benefits for patients. In addition to providing cross-correction by secreting a-gal A enzyme taken up by bystander cells, studies in animal models and humans suggest rapamycin exposure promotes the formation of Tregs, which are critical for keeping autoimmune inflammatory responses systemically attenuated (PMID 31874182). As a result, GLA-T gene therapy has the potential to activate synergistic mechanisms that mitigate the disruptive effects of substrate accumulation in Fabry disease.
