Gene Therapy Strategy Shows Long-Term Correction of Familial Hypercholesterolemia in Preclinical Study
Muscle-targeted approach using helper-dependent adenoviral vectors delivers sustained lipid improvements and reduced atherosclerosis for up to 12 weeks in LDLR-deficient mice
Napoli, Italia, March, 19, 2026 — A new preclinical study published in a leading scientific journal reports a muscle-targeted gene therapy approach for familial hypercholesterolemia (FH), a severe inherited disorder most commonly caused by mutations in the LDL receptor (LDLR) gene.
Researchers developed helper-dependent adenoviral (HD-Ad) vectors encoding a fusion protein consisting of the extracellular domain of LDLR linked to transferrin, designed for selective expression in skeletal muscle.
In laboratory experiments, the therapy restored LDL uptake in LDLR-i cells in vitro.
In a mouse model of LDLR deficiency, a single intramuscular administration resulted in:
- Sustained expression of the therapeutic protein
- Improved lipid profiles lasting up to 12 weeks
- Significant reduction of aortic atherosclerosis
- No major systemic toxicity observed
Together, the findings support the potential of a durable, muscle-directed gene therapy strategy for homozygous FH, particularly for patients who respond inadequately to current lipid-lowering treatments.
“This study shows that a single administration of our muscle-targeted gene therapy can provide long-term improvement in cholesterol metabolism in models of Familial Hypercholesterolemia,” said Maria Vitale, Lead Scientist of the study.
“By enabling skeletal muscle to produce a therapeutic protein derived from the LDLR gene, we observed sustained lipid improvements and a reduction in atherosclerosis for up to a year in preclinical models.”
“Patients with severe Familial Hypercholesterolemia often require lifelong treatment and may still face significant cardiovascular risk,” said Lucio Pastore, Senior Scientist of all the study.
“Our findings suggest that a muscle-directed gene therapy approach could offer a long-lasting treatment option and support further development of gene-based strategies for inherited lipid disorders.”
This work was also supported by EXTEND, the Italian National Technology Transfer Hub dedicated to the biopharmaceutical sector, promoted by CDP Venture Capital in partnership with Evotec.
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