Featured Research

from universities, journals, and other organizations

New cell-based system can screen drug candidates for cardiac toxicity long before they leave lab

Date:
December 17, 2012
Source:
American Society for Cell Biology
Summary:
A new stem cell-derived system for screening experimental drugs for cardiotoxicity could identify dangerous side effects early in the development process, thereby potentially saving time, lives and money. Cardiotoxicity is one of the primary reasons new drugs wash out in preclinical or even full clinical trials. Currently used assays are ineffective at assessing potential adverse interactions with other biochemical or contractile processes.

A new stem cell-derived system for screening experimental drugs for cardiotoxicity could identify dangerous side effects early in the development process, thereby potentially saving time, lives and money, according to Evan F. Cromwell, PhD, of Molecular Devices, LLC, Sunnyvale, CA, in a presentation at the American Society for Cell Biology's Annual Meeting, Dec 17 in San Francisco.

Vioxx is probably the most notorious example of a blockbuster drug removed from the market after FDA approval because of adverse cardiac side effects, Dr. Cromwell explained, but it was not the only drug to fail because of unexpected negative effects on the heart.

Cardiotoxicity remains one of the primary reasons new drugs wash out in preclinical or even full clinical trials, he said. There is often a huge cost for these failures, both to the pharmaceutical companies whose long-term investments can be wiped out in a single study and to consumers who face the risk of unintended harm.

Currently cardiotoxicity is detected using electrophysiology-based assays for interactions of compounds with potassium ion channels. However, available assays are not effective at assessing potential adverse interactions with other biochemical or contractile processes.

The need for better cardiotoxicity assays more predictive of myocardial performance led Dr. Cromwell, Oksana Sirenko, PhD, and colleagues at the California biotech, Molecular Devices, to develop an in vitro system that employs stem cell-derived cardiomyocytes to screen for potential adverse cardiac effects.

Stem cell-derived cardiomyocytes are especially suitable for an in vitro system, Dr. Cromwell explains, because they express ion channels vital for the cardiomyocytes' function and demonstrate spontaneous mechanical and electrical activity similar to that of native cardiac cells. When these cultured cardiomyocytes form a confluent layer and reach sufficient maturity, they begin to contract spontaneously. The team then employs a fast kinetic fluorescence imaging method to monitor fluctuations in intracellular calcium ion (Ca2+) levels during contractions. This provides a direct assessment of Ca2+ handling with surrogate assessments of electrophysiological activity in the muscle cell membrane and beat rate.

Phenotypic deviations from normal contractions that can be measured in the improved assay include beat rate, peak width and pattern irregularities. This multiparametric characterization of a compound's perturbation of cardiomyocyte contractions can also yield insights into mechanisms of action (MOA).

Dr. Cromwell reports, "We have characterized numerous pharmacological compounds and detected concentration-dependent modulation of beating rate and atypical patterns consistent with their MOA." This assay shows great promise to exclude preclinical candidates that have cardiotoxicity or other cardio safety issues, according to Dr. Cromwell.


Story Source:

The above story is based on materials provided by American Society for Cell Biology. Note: Materials may be edited for content and length.


Cite This Page:

American Society for Cell Biology. "New cell-based system can screen drug candidates for cardiac toxicity long before they leave lab." ScienceDaily. ScienceDaily, 17 December 2012. <www.sciencedaily.com/releases/2012/12/121217140529.htm>.
American Society for Cell Biology. (2012, December 17). New cell-based system can screen drug candidates for cardiac toxicity long before they leave lab. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2012/12/121217140529.htm
American Society for Cell Biology. "New cell-based system can screen drug candidates for cardiac toxicity long before they leave lab." ScienceDaily. www.sciencedaily.com/releases/2012/12/121217140529.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins