The purpose of this study is to test how different doses of a statin, Lipitor, affect muscle
health and function, and cardiovascular fitness.

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder
characterized by absent or severely reduced capacity to catabolize circulating LDL particles
by the hepatic LDL receptor. As a consequence, HoFH subjects present abnormal total plasma
cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset
of cardiovascular disease. Early initiation of aggressive treatment for these patients is
therefore essential. Unfortunately, despite existing therapies, treated LDL-C levels could
remain well above acceptable levels. 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. This first-in-humans study is intended
to evaluate the safety of this gene therapy investigational product and assess preliminary
evidence of efficacy using plasma LDL-C levels as a surrogate biomarker for human LDLR
transgene expression.