Galactose-1-phosphate uridylyltransferase (GALT) (GALT)

Galactose-1-phosphate uridylyltransferase (GALT) is a critical metabolic enzyme that facilitates the second step of the Leloir pathway, converting galactose-1-phosphate and UDP-glucose into UDP-galactose and glucose-1-phosphate (UniProt P07902). Mutations in the GALT gene lead to Classic Galactosemia, a rare and potentially fatal metabolic disorder characterized by the toxic accumulation of galactose metabolites, which causes multi-organ damage including liver dysfunction, cataracts, and neurodevelopmental delays (NIH GARD). While dietary restriction of galactose is the current standard of care, it often fails to prevent long-term complications like cognitive impairment and primary ovarian insufficiency. AAV-mediated gene delivery, such as the LX2020 program, represents a novel therapeutic modality designed to restore endogenous GALT activity by delivering a functional transgene to the liver (Lexeo Therapeutics). This approach aims to achieve sustained reduction of toxic biomarkers like erythrocyte galactose-1-phosphate (Gal-1-P) and provide a more comprehensive treatment for the underlying metabolic defect (PubMed 33403340). Safety considerations for this target include the potential for AAV-related hepatotoxicity and the development of neutralizing antibodies that may limit the efficacy or redosing of the gene therapy.

Other names

Galactose-1-phosphate uridylyltransferaseUDP-glucose--hexose-1-phosphate uridylyltransferaseGal-1-P uridylyltransferaseGalactose-1-phosphate uridyltransferaseGALT

AAV-mediated gene replacement therapy designed to restore functional GALT enzyme activity and normalize the Leloir pathway.