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.

Related Articles


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 While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in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 March 3, 2015 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 March 3, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Tuesday, March 3, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

This Nasal Treatment Could Help Ease Migraine Pain

This Nasal Treatment Could Help Ease Migraine Pain

Newsy (Mar. 2, 2015) — Researchers gave lidocaine to 112 patients, and about 88 percent of the subjects said they needed less migraine-relief medicine the next day. Video provided by Newsy
Powered by NewsLook.com
How Facebook Use Can Lead To Depression

How Facebook Use Can Lead To Depression

Newsy (Mar. 1, 2015) — Margaret Duffy of the University of Missouri talks about her study on the social network and the envy and depression that Facebook use can cause. Video provided by Newsy
Powered by NewsLook.com
The Best Foods to Battle Stress

The Best Foods to Battle Stress

Buzz60 (Feb. 26, 2015) — If you&apos;re dealing with anxiety, there are a few foods that can help. Krystin Goodwin (@krystingoodwin) has the best foods to tame stress. Video provided by Buzz60
Powered by NewsLook.com
Sleeping Too Much Or Too Little Might Increase Stroke Risk

Sleeping Too Much Or Too Little Might Increase Stroke Risk

Newsy (Feb. 26, 2015) — People who sleep more than eight hours per night are 45 percent more likely to have a stroke, according to a University of Cambridge study. 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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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