Featured Research

from universities, journals, and other organizations

Compound That Frees Trapped Cholesterol Identified

Date:
January 30, 2009
Source:
UT Southwestern Medical Center
Summary:
Researchers have identified in mice a compound that liberates cholesterol that has inappropriately accumulated to excessive levels inside cells.

Dr. John Dietschy (right), along with colleagues Drs. Benny Liu and Joyce Repa, have identified a compound that liberates cholesterol that has inappropriately accumulated to excessive levels inside cells. This cholesterol accumulation is a characteristic of Niemann-Pick type C disease.
Credit: Image courtesy of UT Southwestern Medical Center

Researchers at UT Southwestern Medical Center have identified in mice a compound that liberates cholesterol that has inappropriately accumulated to excessive levels inside cells.

Related Articles


The findings shed light on how cholesterol is transported through the cells of the body and suggest a possible therapeutic target for Niemann-Pick type C disease (NP-C), an inherited neurodegenerative disorder characterized by abnormally high cholesterol levels in every organ.

“What we’ve shown is that very quickly after administration of this compound, the huge pool of cholesterol that has just been accumulating in the cells is suddenly released and metabolized normally,” said Dr. John Dietschy, professor of internal medicine at UT Southwestern and senior author of the study appearing online this week and in an upcoming issue of the Proceedings of the National Academy of Sciences. “With just one dose, you excrete a large portion of this pool of cholesterol.”

Cholesterol in the body comes from dietary sources and is also made by the body itself. It is essential for many biological processes, including the construction and maintenance of cell membranes. Cholesterol normally is transported through cells and is excreted by the body.

People with Niemann-Pick type C have a genetic mutation that causes excessive amounts of cholesterol to accumulate in compartments within cells called lysosomes. This cholesterol accumulation leads to liver disease, neurodegeneration and dementia. There is no specific level at which cholesterol levels become abnormal, but the vast majority of children diagnosed with NP-C die before they are 20 years old and many before age 10. Late onset of neurological symptoms such as clumsiness, mild retardation and delayed development of fine motor skills can lead to longer life spans, but few people diagnosed with NP-C reach age 40.

In the current research, researchers injected a single dose of a cholesterol-binding agent known as CYCLO into 7-day-old mice with the Niemann-Pick mutation. Shortly after administration, the mice that received CYCLO began to process cholesterol just as their healthy counterparts did. After 49 days, the mice treated with a single injection continued to show substantially lower tissue cholesterol levels than the untreated mice, as well as improved liver function and decreased neurodegeneration.

Dr. Dietschy, who has been studying cholesterol metabolism for nearly 50 years, cautioned that the findings in no way represent a Niemann-Pick disease cure.

“The key idea is that we appear to have overcome the transport defect in the lysosome that is brought about by the genetic defect or mutation,” Dr. Dietschy said. “We do not yet understand what is happening at the molecular level, but it is clear that this compound somehow overcomes the genetic defect that causes individuals to accumulate cholesterol.”

The next step in Dr. Dietschy’s investigation is to determine the concentration of CYCLO needed to trigger the cholesterol’s release. Researchers also hope to determine in animals the additional lifespan CYCLO administration provides, as well as how long the drug’s affects lasts.

“By treating at seven days, we eliminated approximately one-third of the accumulated cholesterol almost immediately,” Dr. Dietschy said. “Now we want to see what happens if we give it every week. Can we maintain low cholesterol levels? That’s what we’re looking at now.”

Other UT Southwestern researchers involved in the research were Dr. Benny Liu, lead author of the study and postdoctoral researcher in internal medicine; Dr. Stephen Turley, professor of internal medicine; Dr. Dennis Burns, professor of pathology; Anna Miller, student research assistant; and Dr. Joyce Repa, assistant professor of physiology.

The work was funded by the U.S. Public Health Service, the Harry S. Moss Heart Trust, the Ara Parseghian Medical Research Foundation and the Dana’s Angels Research Trust.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

UT Southwestern Medical Center. "Compound That Frees Trapped Cholesterol Identified." ScienceDaily. ScienceDaily, 30 January 2009. <www.sciencedaily.com/releases/2009/01/090126173717.htm>.
UT Southwestern Medical Center. (2009, January 30). Compound That Frees Trapped Cholesterol Identified. ScienceDaily. Retrieved March 29, 2015 from www.sciencedaily.com/releases/2009/01/090126173717.htm
UT Southwestern Medical Center. "Compound That Frees Trapped Cholesterol Identified." ScienceDaily. www.sciencedaily.com/releases/2009/01/090126173717.htm (accessed March 29, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, March 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
WH Plan to Fight Antibiotic-Resistant Germs

WH Plan to Fight Antibiotic-Resistant Germs

AP (Mar. 27, 2015) The White House on Friday announced a five-year plan to fight the threat posed by antibiotic-resistant bacteria amid fears that once-treatable germs could become deadly. (March 27) Video provided by AP
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) 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:

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