Cells instead of a pacemaker: difficult, dangerous, but possible
Electronic heart rate drivers introduced into medical practice in the 1970s saved the lives of millions of patients with cardiac disorders. However, despite constant improvement, the devices used are still far from perfect. Their installation is impossible without surgical intervention, the batteries feeding them are discharged, and the wires running from them to the implant fail.
Scientists at Columbia University (New York), working under the guidance of Dr. Michael Rosen, already in 2001 began work on a promising biological alternative to electronic rhythm drivers.
The idea is to restore the heart's ability to contract by embedding into the cells of regions of the heart that are not capable of regular contractions, genes necessary for the functioning of some cardiomyocytes as pacemakers (pacemakers) – several sections of the heart muscle that supply electrical impulses to neighboring areas. Thanks to them, the heart is able to contract even in the absence of commands from the nervous system.
According to Rosen, electronic rhythm drivers are a very valuable invention, and the technique being developed is not intended to replace electronic devices, but as an alternative method of treatment.
At first, the authors used an adenovirus to embed the necessary gene into cells, infected cells with which (in cell culture conditions) began to contract and form a pulsating electric current.
Testing of the technique on dogs with a slow heart rate was also successful. Embedding the therapeutic gene into animal heart cells increased the rate of heart contractions from 25-40 to 60 beats per minute. The obtained results interested a large company for the production of rhythm drivers Guidant, currently part of Boston Scientific, which signed a small contract with scientists for further research.
Using a cold-causing adenovirus to deliver genes has its drawbacks. The virus causes the infected cell to perceive the embedded gene as its own, but this effect persists for only a few weeks. In addition, deaths during clinical trials of gene therapy using adenovirus indicate the insecurity of this approach.
In 2002, the authors proposed to embed rhythm driver genes into the genome of adult stem cells using a technique that does not require the use of viruses, and then introduce genetically modified cells into the heart. There was a fear that the modified cells would not integrate into the necessary areas of the heart muscle, but would spread through the adjacent tissues with the formation of random foci of contractions. Fortunately, six weeks of observation of dogs who were injected with such cells showed that the modified cells behave exactly as they should.
On The Wall Street Journal website, you can watch two short videos showing how rat heart cells contract before the introduction of pacemaker cells and after the experimental procedure.
As a precautionary measure, the researchers demonstrated that the hyperactivity of such cells can be suppressed with the drug ivabradine, which is allowed in Europe to slow down the heart rate. At this stage, Boston Scientific has allocated a five-year grant to continue research work, within which scientists have been working for more than three years.
When carrying out the work, the authors adhere to the principle of preventing possible problems. Currently, they are working with three cell lines isolated by Cambrex specialists and screened for markers of possible differentiation failures and the likelihood of triggering self-destruction mechanisms.
The next stage of the work is planned one-year clinical trials on dogs, which require additional funding. The University's Technology Transfer Office has already drawn up a business plan for the creation of a subsidiary company and started looking for investors.
Other research groups are also working on the creation of various biological rhythm drivers, but they are all very cautious. The enthusiasm of the researchers somewhat weakened after the death of several participants in clinical trials of various gene therapy methods. Moreover, existing electronic devices work quite well and developers prefer the termination of work to harm the test participants.
However, in the case of positive results of preliminary tests, the advantages of biological pacemakers over electronic ones are obvious.
Portal "Eternal youth" www.vechnayamolodost.ru according to the Wall Street Journal 28.04.2008