Federal Project Grant Award Summary

The University of Texas Southwestern Medical Center received a $456,500 project grant awarded May 1, 2026, by the National Center for Advancing Translational Sciences (NCATS, CFDA 93.350) to conduct preclinical research on AAV9FYHR gene replacement therapy for pyruvate dehydrogenase complex deficiency (PDCD). The grant funds research activities through April 30, 2028, that will evaluate the efficacy and safety of a novel adeno-associated virus 9 variant (AAV9FYHR) vector designed to deliver the PDHA1 gene to the central nervous system in an E75A mouse model of PDHA1 deficiency. The deliverables include characterization of the therapeutic vector's dose-response and age-dependent effectiveness, identification of toxicity profiles, and generation of preclinical evidence to support potential advancement toward clinical trial readiness for this severe rare mitochondrial disorder.

This project advances NCATS's translational science mission by generating proof-of-concept data that bridges basic scientific discovery with clinical application development. Leveraging UT Southwestern's established expertise in gene therapy development—evidenced by eight gene therapy candidates from the institution that have progressed to clinical trials, including two ongoing since 2021—the research will address a critical treatment gap for PDHA1 deficiency, a rare but severe condition with no current curative therapy and a poor prognosis affecting approximately 1 in 50,000 to 75,000 live births in North America.