Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Jefferson scientists use gene therapy to restore function of damaged heart cells in lab


Researchers at Jefferson Medical College and Duke University have used gene therapy to help damaged heart cells regain strength and beat normally again in the laboratory. The work takes the scientists one step closer to eventual clinical trials in humans.

Walter Koch, Ph.D., director of the Center for Translational Medicine of the Department of Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his colleagues at Duke used a virus to carry a gene into the heart cells of individuals who had suffered from congestive heart failure. The gene introduced into these heart cells blocks the activity of an enzyme that is increased in failing human hearts and which contributes to the loss of the heart’s contractile strength during the development of heart failure. When the activity of this enzyme is blocked by the gene therapy, the heart cells were able to contract at normal strength and their overall performance was improved.

Dr. Koch and his co-workers at Duke University Medical Center in Durham, N.C., report their findings April 6, 2004, in Circulation, a journal of the American Heart Association.

According to Dr. Koch, who is W.W. Smith Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, researchers have known for some time that the beta-adrenergic receptor system fails to work properly in individuals with congestive heart failure. Such receptors "drive the heart – both by rate and force of contraction," he says.

The researchers’ target has been the beta-adrenergic kinase (ßARK1), an enzyme that is elevated in human heart failure. One of its functions is to turn off beta-adrenergic receptors. "In heart failure, beta adrenergic receptor density is decreased, ßARK is increased and both together cause dysfunctional beta receptor signaling," Dr. Koch says. "A failing heart then has little capacity to respond to exercise or stress because there are fewer receptors and the remaining receptors are more or less turned off.

"We have thought that inhibiting ßARK activity could increase signaling and increase function," he explains. In the laboratory dish, the researchers infected heart cells from patients who underwent cardiac transplantation due to end-stage heart failure with an adenovirus that encoded both ßARKct – a peptide that can block ßARK – and a so-called "reporter gene" protein, which glows green. The latter provided a signal to the scientists that the inhibitor was indeed present in the heart cells. They then were able to use a video camera to actually measure how strong the individual heart cells were beating. The virus used in this study is a version of the common cold virus that has been rendered non-infectious and serves to carry the therapeutic gene to the failing heart cells.

"We put the ßARKct into the cells, and failing human hearts become more like normal hearts, based on their ability to contract and other functional properties of these cells was also improved," Dr. Koch says. "This is the first work in actual human hearts to show efficacy of ßARKct as a potential therapy and more importantly, proves that the enzyme ßARK1 is a target for heart failure treatment."

"This study is the last proof of concept," he adds, noting that years of previous work in various animal models enabled the research team to reach this point. "Now we are dealing with human cells from failing human hearts," he says, noting that essentially these studies in human heart cells "confirm all we have done."

Congestive heart failure affects nearly 5 million Americans, many of whom have poor long-term prognoses, despite recent therapeutic advances. Dr. Koch hopes that such studies will move gene therapy forward as a viable option for heart failure patients. He notes that pre-clinical studies in "clinically relevant" large animal models are progressing, and should eventually lead to human trials using the ßARKct gene.

Steve Benowitz | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

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: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>