Familial Hypercholesterolemia

Familial Hypercholesterolemia (FH) is characterized by high total cholesterol levels and high low density lipoprotein (LDL), or “bad cholesterol” levels, and patients with FH are at an increased risk for developing atherosclerosis and early death. FH is caused by defects in the gene encoding the LDL receptor, which removes LDL from the bloodstream. Patients homozygous for the defect (carrying two defective copies) are at a high risk of developing cardiovascular disease in childhood; patients who are heterozygous for the defect (carry one defective copy and one normal copy) develop premature atherosclerosis in adulthood.

Status

Current therapies for FH include treating the patient with statins, which increase expression of any functional LDL receptor, and LDL apheresis, in which the blood is routinely filtered to remove excess LDL. Gene therapy for FH involves delivering a normal copy of the LDL receptor gene to the liver, allowing the liver to remove and metabolize circulating LDL. AAV8 is significantly more efficient in delivering genes to the liver than other serotypes, and more efficient than other gene therapy delivery systems such as lentivirus. The proposed therapeutic is in the preclinical stage of development.

Market

Homozygous FH is rare, affecting 1 in 1,000,000 individuals; however, heterozygous FH affects approximately 1 in 500 individuals, or approximately 600,000 in the U.S. The costs and inconvenience of apheresis, and the fact that statins often do not sufficiently control LDL levels indicate that there is a need for a more effective therapy.