HDL Gene Therapy

Coronary heart disease has remained one of the leading causes of death in the United States since the year 1900, according to the U.S. Environmental Protection Agency. The development of plaque deposits along artery passageways accounts for how this condition progresses. HDL gene therapy is, as of yet, an experimental approach designed to provide the body with a gene that works to eliminate cholesterol build-up along artery walls.

Process

• The process behind gene therapy involves transferring a healthy, or modified DNA, gene into a group of target cells in the body, according to the University of Utah. To do this, scientists must first identify the faulty gene, locate which cells in the body contain the gene, and implant the healthy gene into the target cells. In the case of HDL gene therapy, the faulty gene is contained inside the liver cells that produce HDL and LDL carriers in the blood.

  HDLs are high-density lipoproteins, responsible for clearing away excess cholesterol deposits from blood vessel walls. LDLs are low-density lipoproteins that tend to create cholesterol deposits in blood vessels. Individuals with a high level of HDLs in the bloodstream are at a lower risk of developing heart disease than those with a low level, according to the University of Utah.

Gene Transfer

• The gene responsible for HDL liver production is apolipoprotein E (apoE), according to the American Association for the Advancement of Science. A study conducted in February 2000 by the Pasteur Institute in Paris, France injected the apoE gene into the liver cells of mice. Results from the study showed a significant decline in blood cholesterol levels, and an increase in HDL carriers in the blood.

  The apoE gene's works by binding to fat particles in the blood, which are usually LDL carriers holding onto unused cholesterol materials. These materials are then brought back to liver and converted to bile, and excreted through the intestines.

Gene Delivery

• Another study conducted in 2006 by the Cedars-Sinai Medical Center used a mutated version of the HDL gene found in a small number of individuals within Milano, Italy. This gene, called apoliprotein A-I Milano, was found to protect the body from cholesterol-related heart disease conditions. Gene transfer was done through bone marrow transplants performed on mice subjects. The gene delivery method used a signal molecule that targeted macrophages, which are immune system cells designed to ingest foreign materials.

  Macrophages are found inside the plaque deposits that line artery and blood vessel walls. And while their role is to contain plaque deposits, the deposits still remain in place. The apolipoprotein A-I Milano gene was shown to bind with HDL molecules, and increase their ability to remove cholesterol from macrophage cells within blood vessel linings. Once removed, cholesterols are sent to the liver, converted to bile and excreted through the intestines.

  Further developments within the HDL gene therapy field hope to design an injectable form of the gene that can be administered every few years to protect the body against heart disease.