Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First biologic pacemaker created by gene therapy in guinea pigs

12.09.2002


Working with guinea pigs, Johns Hopkins scientists have created what is believed to be the first biologic pacemaker for the heart, paving the way for a genetically engineered alternative to implanted electronic pacemakers. The advance, reported in the Sept. 12 issue of Nature, uses gene therapy to convert a small fraction of guinea pigs’ heart muscle cells into specialized "pacing" cells.



"We now can envision a day when it will be possible to recreate an individual’s pacemaker cells or develop hybrid pacemakers -- part electronic and part biologic," says Eduardo Marbán, M.D., Ph.D., Michel Mirowski professor at Hopkins’ Institute of Molecular Cardiology, adding that clinical applications are still a few years away.

"Most applications of gene therapy try to cure a disease caused by a single defective or missing gene, but we used the cells’ genes as a tool box to tweak its function," adds Marbán. "This is akin to turning a clunky old car into a hot rod -- if you have the parts and expertise, it can be done."


In the Hopkins experiments, heart cells in the guinea pigs spontaneously and rhythmically "fired" after the scientists genetically altered the cells’ balance of potassium. Such a "biopacemaker" is a potentially important option for patients at too high a risk for infection from implanted electronic pacemakers or too small for an implanted device, say the researchers. "A biologic pacemaker should also be able to adjust to the body’s changing needs, whereas an electronic pacemaker, at least in its simplest form, does not," says Marbán. "Anything that normally makes our heart go pitter-pat doesn’t change the steady rhythm of the electronic pacemaker. Instead, people get tired very quickly."

Two tiny sets of "pacing" cells in the heart normally give the organ its regular beat by stimulating other cells to contract. If these specialized cells stop working or die, an implanted electronic pacemaker can keep the heartbeat going, a fact of life for hundreds of thousands of people.

"We’ve created a biologic pacemaker in the guinea pig, but now the hard work comes," says Marbán. "We need to fine tune it -- develop controlling strategies, find the optimum place to re-engineer the cells in the heart, control the frequency of the new pacemaker. But there is light at the end of the tunnel."

In the vast majority of heart muscle cells, a particular channel maintains a balance of potassium that makes it more difficult for them to "fire," so instead of being able to generate electricity on their own, they must be triggered by pacemaker cells.

The Hopkins scientists figured that altering this potassium balance might allow heart cells to regain the ability to fire without being triggered. Others had discovered a number of years ago that if just three specific building blocks of heart cells’ potassium channel (called the "inward rectifier potassium current") are altered, the potassium balance is disrupted.

The Hopkins scientists attached the gene for the defective channel to a virus, and also tacked on green fluorescent protein so infected cells would be easily identifiable. Virus-infected cells faithfully transcribe genes carried by the virus.

"This potassium channel acts like an anchor, keeping heart muscle cells from developing pacemaker-like abilities," says Marbán. "By blocking the channel, we effectively lifted the anchor, freeing the muscle cells to re-establish abilities they last held in the developing embryo."

Three to four days after injecting the gene-carrying virus into the heart muscle of guinea pigs, Junichiro Miake, Ph.D., then a postdoctoral fellow at Hopkins, saw that heart cells had begun making the defective potassium channel. Even more important, a new, faster, pace-setting impulse was clearly visible on electrocardiograms from the animals.

"When this channel is blocked, heart muscle cells that normally have to wait for stimulation begin to beat on their own," says Marbán. "In many important ways the guinea pig is similar to humans. Its cardiac electrophysiology is very similar, and this channel is as common in human heart muscle as in the guinea pig. We believe the same principles will prevail in humans."

Normally, one set of 1,000 to 3,000 pacemaker cells is found in the right upper chamber, or atrium, of the heart, and one set straddling the junction between the atrium and the lower chamber, or ventricle. Damage to either set of pacemaker cells or the connection between them can require an electronic pacemaker. About 250,000 electronic pacemakers, about the size of a personal digital assistant (PDA), are implanted each year in the U.S.


###

Joanna Downer | EurekAlert!
Further information:
http://www.nature.com/nature
http://www.nhlbi.nih.gov

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Did you know how many parts of your car require infrared heat?

23.10.2017 | Automotive Engineering

3rd Symposium on Driving Simulation

23.10.2017 | Event News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>