Gene therapy of atherosclerosis is almost not fiction

Gene therapy has defeated high cholesterolAlexey Tymoshenko, GZT.RU
Predisposition to cardiovascular diseases can be eliminated by gene therapy.

The hereditarily elevated cholesterol level could be eliminated by replacing only one gene – however, so far only in an experiment on laboratory animals.

The results of the work of scientists from the University of Pennsylvania made it possible to turn gene therapy of atherosclerosis from an absolutely fantastic idea into just a "semi–fantastic" one - the researchers showed that such manipulations are possible in principle. For the treatment of other diseases (congenital blindness, for example), gene therapy has already been used in humans.

How Gene Therapy WorksThe idea of gene therapy is based on the fact that a number of diseases are caused by the fact that a person receives an unsuccessful set of genes from his parents at conception.

For example, the gene encoding the protein necessary for the normal functioning of retinal cells turns out to be damaged – the carrier of such a gene turns out to be blind from birth.

A gene is a fragment of DNA, and additional sections can be inserted into DNA, and even without involving micropipettes and nanorobots – the insertion of genes is carried out by viruses during their reproduction. You can take a virus, remove the genes that cause the disease from there, and send them to infect cells: the virus will embed additional material into their DNA on its own.

This is how virus therapy works – viruses are remade in order to,
to embed genes without causing disease.
Even HIV can be used to treat diseases.

The additional gene will be the one that is needed to restore the cell to normal operation: in general, it is like if a number of workshops that received incorrect orders were sent the correct drawings instead of defective ones. Does the body produce a defective protein? Gene therapy will eliminate this by setting up production anew.

Cholesterol, genes and blood vessels

A heart attack is caused by blood clots that have torn off and clogged the vessels of the heart muscle. If a vessel leading to the brain is blocked, it is a stroke. Blockage of vessels of other organs also does not pass without a trace.

Blood clots are formed not by chance, but in place of cholesterol plaques – deposits on the walls of blood vessels of cholesterol, a substance in demand in many processes, from the growth of nerve cells to the production of hormones. Normally, cholesterol should not be deposited anywhere, but in practice it often turns out differently.

An artery clogged with atherosclerosis, a cross-section under a microscope.
A little more – and it will be completely blocked

Other substances play a key role in the growth of cholesterol plaques – low-density lipoproteins, or LDL, for short. LDL is protein molecules that carry cholesterol throughout the body (a process, we emphasize, absolutely normal and necessary), acting as a kind of couriers.

LDL is guided by the presence of special receptors in cells that receive their cargo – cholesterol molecules. There is a receptor – cholesterol is transmitted as intended. There are no receptors or the receptor is not identified as correct – the cargo is dumped anywhere, just as careless garbage truck drivers dump garbage outside the landfill.

The cholesterol receptor in the schematic image looks like a piece of bent wire.
Normally, this protein is located inside the cell membrane
and is responsible for the transfer of cholesterol from the blood to consumers

The LDLR cholesterol receptor defect is one of the possible causes of clogging of blood vessels and their overlap with atherosclerotic plaques, and it has been studied quite well. Genetic engineering methods have even produced mice that do not have this receptor: such rodents earn atherosclerosis already at the age of two months. Or, if you count the mouse age in human years – by about 20 years.

Therapy

To overcome congenital hypercholesterolemia, scientists took the AAD8 virus, belonging to the family of adenoassociated viruses. It has previously been shown that it is practically harmless to humans and, in addition, embeds its genes into DNA not randomly, but into certain fragments of the 19th chromosome. (A random insertion of a gene into an arbitrary place in the DNA can with a negligible probability lead to a mutation that turns a normal cell into a malignant one.)

By embedding the missing gene into the virus, the researchers infected experimental mice – a solution with AAD8 was injected intravenously, that is, through the tail (it is in the tail of mice that a vein passes, where it is relatively easy to get a needle). After the injection, biologists waited 35 days, and then sent the rodents for tests, from which they did not return, since further studies required not just a blood test, but also a study of the aortic walls.

The sacrifices were not in vain. There were significantly fewer atherosclerotic plaques on the walls of the largest vessel, literally dozens of times. Now it remains to prove the safety and effectiveness of the method – after which, perhaps, after the detection of abnormal cholesterol levels in the blood, an injection of the virus will be prescribed.

Portal "Eternal youth" http://vechnayamolodost.ru20.10.2010