Treatment of glutaric aciduria type I (GA-I) via intracerebroventricular delivery of GCDH.

ABSTRACT: Glutaric aciduria type I (GA-I) is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase (GCDH). Patients who do not receive proper treatment may die from acute encephalopathic crisis. Current treatments for GA-I include a low-lysine diet combined with oral supplementation of L-carnitine. A mouse model of Gcdh ^{c.422_428del/c.422_428del} (Gcdh ^-/-) was generated in our laboratory using CRISPR/Cas9. Gcdh ^-/- mice had significantly higher levels of glutaric acid (GA) in the plasma, liver, and brain than those in wild-type C57BL/6 mice. When given a high-protein diet (HPD) for two days, approximately 60% of Gcdh ^-/- mice did not survive the metabolic stress. To evaluate whether GCDH

SUBMITTER: Guo L 

PROVIDER: S-EPMC11197790 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature