Featured Research

from universities, journals, and other organizations

Potential therapy for human prion disease

Date:
April 3, 2013
Source:
Scripps Research Institute
Summary:
Scientists have for the first time identified a pair of drugs already approved for human use that show anti-prion activity and, for one of them, great promise in treating rare and universally fatal disorders, such as Creutzfeldt-Jakob disease, caused by misfolded proteins called prions.

Human diseases caused by misfolded proteins known as prions are some of most rare yet terrifying on the planet -- incurable with disturbing symptoms that include dementia, personality shifts, hallucinations and coordination problems. The most well-known of these is Creutzfeldt-Jakob disease, which can be described as the naturally occurring human equivalent of mad cow disease.

Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time identified a pair of drugs already approved for human use that show anti-prion activity and, for one of them, great promise in treating these universally fatal disorders.

The study, led by TSRI Professor Corinne Lasmιzas and performed in collaboration with TSRI Professor Emeritus Charles Weissmann and Director of Lead Identification Peter Hodder, was published this week online ahead of print by the journal Proceedings of the National Academy of Sciences.

The new study used an innovative high-throughput screening technique to uncover compounds that decrease the amount of the normal form of the prion protein (PrP, which becomes distorted by the disease) at the cell surface. The scientists found two compounds that reduced PrP on cell surfaces by approximately 70 percent in the screening and follow up tests.

The two compounds are already marketed as the drugs tacrolimus and astemizole. Tacrolimus is an immune suppressant widely used in organ transplantation. Tacrolimus could prove problematic as an anti-prion drug, however, because of issues including possible neurotoxicity.

However, astemizole is an antihistamine that has potential for use as an anti-prion drug. While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in more than 30 countries and has a well-established safety profile. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration.

Lasmιzas noted that astemizole appears to stimulate autophagy, the process by which cells eliminate unwanted components. "Autophagy is involved in several protein misfolding neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases," she said. "So future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders."

The study noted that eliminating cell surface PrP expression could also be a potentially new approach to treat Alzheimer's disease, which is characterized by the build-up of amyloid β plaque in the brain. PrP is a cell surface receptor for Aβ peptides and helps mediate a number of critical deleterious processes in animal models of the disease.

The first author of the study, "Unique Drug Screening Approach for Prion Diseases Identifies Tacrolimus and Astemizole as Antiprion Agents," is Yervand Eduard Karapetyan of The Scripps Research Institute. Other authors include Gian Franco Sferrazza, Minghai Zhou, Gregory Ottenberg, Timothy Spicer, Peter Chase, Mohammad Fallahi, Peter Hodder and Charles Weissmann of The Scripps Research Institute.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Y. E. Karapetyan, G. F. Sferrazza, M. Zhou, G. Ottenberg, T. Spicer, P. Chase, M. Fallahi, P. Hodder, C. Weissmann, C. I. Lasmezas. Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1303510110

Cite This Page:

Scripps Research Institute. "Potential therapy for human prion disease." ScienceDaily. ScienceDaily, 3 April 2013. <www.sciencedaily.com/releases/2013/04/130403154305.htm>.
Scripps Research Institute. (2013, April 3). Potential therapy for human prion disease. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2013/04/130403154305.htm
Scripps Research Institute. "Potential therapy for human prion disease." ScienceDaily. www.sciencedaily.com/releases/2013/04/130403154305.htm (accessed August 22, 2014).

Share This




More Mind & Brain News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) — According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Charter Schools Alter Post-Katrina Landscape

Charter Schools Alter Post-Katrina Landscape

AP (Aug. 20, 2014) — Nine years after Hurricane Katrina, charter schools are the new reality of public education in New Orleans. The state of Louisiana took over most of the city's public schools after the killer storm in 2005. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) — Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
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