Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. The most frequent cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL apheresis. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial. No study drug will be administered in this screening study.

Inclusion criteria

• Males and females ≥ 18 years of age
• Clinical presentation consistent with homozygous FH
• Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form

Exclusion criteria

• Known to carry confirmed mutations in genes affecting LDL receptor functionality other than the LDLR gene
• History of cirrhosis based on documented histological evaluation or non-invasive imaging
• Documented diagnosis of any of the following liver diseases: Hepatitis B or C; Biopsy-proven nonalcoholic steatohepatitis; Biopsy-proven alcoholic liver disease; Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis; Wilson's disease; Hemochromatosis; alpha1 anti-trypsin deficiency
• History of immunodeficiency diseases, including a positive HIV test result
• Previous organ transplantation
• Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study
• Inability to participate