News | February 06, 2015

Novel Peptide Shows Promise Regenerating Cardiac Nerves and Averting Arrhythmias

Peptide used to treat spinal-cord injuries found to penetrate heart attack scar tissue

February 6, 2015 — Case Western Reserve’s chemical compound aimed at restoring spinal cord function may have an additional purpose: stopping potentially fatal arrhythmias after heart attack.

Case Western Reserve neurosciences professor Jerry Silver, Ph.D., long has believed that lessons learned over decades from spinal cord research could someday apply to other areas of the body. He got the chance to test his theory when a colleague from another campus realized that his new compound — intracellular sigma peptide (ISP) — could address a critical cardiac issue.

The results of the project, led by Oregon Health & Sciences University (OHSU) researcher Beth A. Habecker, Ph.D., exceeded even Silver’s greatest hopes: 100 percent success in animal models. Details can be found in the Feb. 2 edition of Nature Communication.

“Essentially, the OHSU group cured arrhythmia in the mouse using ISP,” Silver said. “They observed true regeneration right back into the scar within the infarct area. This is pretty exciting.”

Habecker, professor and interim chair of OHSU’s physiology and pharmacology department, is similarly enthusiastic about the findings. “Patients who survive a heart attack remain at high risk for cardiac arrest and severe arrhythmias,” explained Habecker, the paper’s senior author. “Recent clinical studies suggest sympathetic denervation predicts the risk for cardiac arrest. Our study shows that this risk can be decreased by intervening with ISP to promote axon regeneration into the cardiac scar.”

At first, the idea sounds counterintuitive: A peptide shown to restore function in spinal cords could help stop an active malfunction in hearts. But once researchers looked more carefully at the reasons for the respective problems, ISP’s benefits to both became clear. Spinal paralysis and denervation in the heart each stem from failed nerve regeneration caused by a family of inhibitory molecules called proteoglycans that form in scar tissue following injury or even the trauma of a cardiac procedure. ISP’s role is to revive those nerves by allowing them to ignore the repulsing scar molecules.

The Nature Communications paper reflects work done entirely at OHSU after Silver’s lab provided enough of the compound for Habecker’s team to perform their experiment. The effort involved simulating the impact of an actual heart attack in mice, and then “treating” it with the ISP, saline or a non-therapeutic peptide (the control).

Two weeks later, the OHSU scientists found that all of the mice that received ISP regained normal levels of sympathetic cardiac nerve function throughout the left ventricle, including the heart attack-damaged areas. Additionally, telemeter readings on these animals showed no arrhythmia activity. In contrast, animals treated with saline or the control peptide had cardiac sympathetic denervation in areas of their hearts damaged by the myocardial infarction, and as a consequence, experienced arrhythmias.

“My role was that of a supplier,” Silver said. “It was really important that this study of the peptide be conducted without my involvement. The study at OHSU provided independent validation that the peptide works in animals. And it confirmed the effectiveness of ISP in a completely different model — heart attack. That kind of replication is rare.”

The discovery has significant potential in heart attack treatment. Currently, 7 to 10 percent of people die within the first six months from sudden cardiac death due to arrhythmia. ISP shows promise in serving as the basis for prophylactic treatment to prevent arrhythmia within the first months of a heart attack.

Next steps in moving ISP forward will be testing the peptide as a post-heart attack treatment in larger animals. Such tests would reveal maximum tolerated dose, any toxicity potential and the extent to which the peptide infiltrates scar tissues. Additionally through animal studies, investigators wish to learn whether ISP administered several months, or even years, after a heart attack would confer a similar benefit as treatment administered three days post-heart attack.

For more information: www.casemed.case.edu

Related Content

Heart Failure Market to Surpass $16 Billion by 2026
News | Heart Failure| September 19, 2017
The heart failure space across the seven key markets of the U.S., France, Germany, Italy, Spain, the U.K. and Japan is...
Heart Failure Patients, Clinicians Have Differing Perceptions of Risk Level
News | Heart Failure| September 06, 2017
September 6, 2017 — Physicians identified a majority of patients with advanced...
Israeli Hospital Completes First Implant of CORolla Heart Failure Device
News | Heart Failure| September 05, 2017
Rambam Hospital in Haifa, Israel, recently became the first to use the CORolla device from Israeli start-up company...
Abbott Receives FDA Approval for HeartMate 3 Left Ventricular Assist System
Technology | Ventricular Assist Devices (VAD)| August 29, 2017
Abbott announced it has received U.S. Food and Drug Administration (FDA) approval for its Full MagLev HeartMate 3 Left...
Sponsored Content | Videos | Cardiovascular Ultrasound| August 28, 2017
This video educational session, provided in partnership with the American Society of Echocardiography (ASE), is title
Biotronik Announces U.S. Launch of Edora HF-T QP CRT Pacemaker
Technology | Cardiac Resynchronization Therapy Devices (CRT)| August 21, 2017
Biotronik announced U.S. Food and Drug Administration (FDA) approval and commercial availability of Edora HF-T QP, an...
New Jersey Researcher Exploring New Stem Cell Therapies for Heart Attacks
News | Stem Cell Therapies| August 04, 2017
In petri dishes in her campus laboratory at New Jersey Institute of Technology, Alice Lee is developing colonies of...
Registry Identifies Early Onset of Heart Failure and Lack of Defibrillators in Asia
News | Heart Failure| August 03, 2017
August 3, 2017 — The Asian Pacific Society of Cardiology (ASPC) held its first-ever late-breaking...
Left Atrial Pressure Monitor from Vectorious Medical Technologies Offers New Hope for Heart Failure Patients

On of the top stories in July was the introduction of a left atrial pressure monitor from Vectorious Medical Technologies to prevent heart failure patient hospitalizations or readmissions. Read the article"Left Atrial Pressure Monitor Offers New Hope for Heart Failure Patients."

Feature | August 01, 2017 | Dave Fornell
Aug.
Overlay Init