Helper-dependent adenoviral vector-mediated expression of an LDL receptor/transferrin chimeric protein in muscle safely reduces atherosclerosis in LDLR-deficient mice - PubMed
6 days ago
- #gene therapy
- #LDL receptor
- #atherosclerosis
- Familial hypercholesterolemia (FH) is caused by LDL receptor mutations, leading to LDL accumulation and cardiovascular disease.
- Current treatments like statins, PCSK9 inhibitors, and bempedoic acid are often insufficient for homozygous FH patients with null LDLR mutations.
- Researchers developed helper-dependent adenoviral vectors expressing LDLR/transferrin chimeric proteins (human and murine versions) driven by a muscle-specific promoter.
- The chimeric proteins restored LDL uptake in LDLR-deficient cells in vitro.
- A single intramuscular injection of the HD-Ad vector in LDLR-deficient mice improved lipid profiles and reduced aortic atherosclerosis for 12 months without major toxicity.
- This strategy shows promise as a potential therapy for FH patients.