Familial Hypercholesterolemia
Conditions
Keywords
familial hypercholesterolemia, inborn errors of metabolism, rare disease
Brief summary
OBJECTIVES: I. Develop an approach for treating patients with homozygous familial hypercholesterolemia using gene therapy with autologous hepatocytes transduced with a normal low-density lipoprotein receptor gene.
Detailed description
PROTOCOL OUTLINE: Autologous hepatocytes are obtained from a partial hepatectomy and transduced with a recombinant retroviral vector containing the low-density lipoprotein receptor gene. The transduced hepatocytes are infused via the inferior mesenteric vein 3 days following surgery. Traditional therapy is discontinued for 4 weeks prior to protocol therapy and may resume 6 weeks after the hepatocyte infusion.
Interventions
PROCEDUREgene therapy
Sponsors
University of Pennsylvania
National Center for Research Resources (NCRR)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
0 Years to No maximum
Healthy volunteers
No
Inclusion criteria
PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Homozygous familial hypercholesterolemia, i.e.: Low-density lipoprotein (LDL) cholesterol greater than 500 mg/dL Autosomal dominant inheritance Early-onset tendon and tuberous xanthomas LDL receptor negative, i.e.: Receptor binding in cultured fibroblasts no more than 20% of normal OR Genotype with 2 previously described, disease-causing alleles Advanced coronary heart disease with relatively poor prognosis, i.e: Angina pectoris History of myocardial infarction Positive exercise tolerance test Atherosclerotic disease in proximal aorta or coronary arteries by ultrasound or angiogram None of the following: Unstable angina pectoris Left ventricular ejection fraction less than 30% Decompensated congestive heart failure Untreated ventricular tachycardia Moderate to severe aortic stenosis Other dyslipidemia Obstructive hepatobiliary disease * Prior/Concurrent Therapy At least 2 weeks since the following: Drugs affecting cholesterol metabolism Plasma exchange LDL apheresis --Patient Characteristics-- Age: Any age Renal: No azotemia No significant proteinuria Other: No hypothyroidism No diabetes
Outcome results
None listed