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 Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

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: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

Beyond the limits of conventional electronics: stable organic molecular nanowires

24.05.2018 | Power and Electrical Engineering

These could revolutionize the world

24.05.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>