SDSU Researchers Discover How To Avoid Liver Injury Caused By Certain

liver411

SDSU Researchers Discover How To Avoid Liver Injury Caused By Certain
Cholesterol-Fighting Drugs

Article Date: 07 Oct 2006 - 0:00am (PDT)

San Diego State University researchers have discovered that blocking the
activity of two genes that control the production of lipoproteins reduces
blood levels of "bad cholesterol" without causing fat retention in the
liver.

This discovery provides new opportunities to develop drugs shown to be
effective in reducing bad cholesterol and heart disease, but without the
unacceptable side effect of fatty deposits on the liver. The discovery is
published in the Oct. 6 issue of the Journal of Biological Chemistry.

Funded by the National Institutes of Health, SDSU Heart Institute
researchers Roger Davis, Nathan Spann and other team members found that by
inhibiting two proteins, microsomal triglyceride transfer protein (MTP) and
liver fatty acid-binding protein (L-FABP), liver production of lipoproteins,
or the protein-coated packages that carry fat and cholesterol through the
bloodstream, can be blocked without causing triglycerides to build on the
liver. Normally, these two complementary proteins work together to produce
fat and package it into lipoproteins.

Prior to this discovery, pharmaceutical company researchers proved that MTP
controlled liver production of lipoproteins. In the 1990s, several drug
companies developed MTP inhibitors which were effective in reducing blood
levels of bad cholesterol in animals and in humans. Initially, the discovery
of MTP inhibitors was seen as a "magic bullet" to reduce heart disease
characterized by hardening of the arteries. However, it was discovered that
MTP inhibitors also caused fatty liver and could not be used safely in
humans and their further development was discontinued.

"This discovery will resurrect the drug development of MTP inhibitors, so
they can be used safely and effectively to lower cholesterol in combination
with L-FABP inhibitors," Davis, who has been working toward this discovery
for 30 years, said. "Additionally, MTP inhibitors appear to be more
effective and more easily tolerated than statins."

Statins are the most commonly used drugs for reducing bad cholesterol in
blood. They work by removing bad cholesterol from the blood, whereas MTP
inhibitors work by blocking its production by the liver. There are some
individuals who cannot tolerate statins or do not respond to treatment.

Currently, Davis and Spann, a recent graduate of the SDSU/University of
California, San Diego joint doctoral program in cell and molecular biology,
are conducting experiments on developing dual MTP/L-FABP inhibitors.

Additionally, San Diego State University Research Foundation has already
filed a patent for their discovery.

"Being a part of a discovery that someday might help human disease is one of
the most rewarding aspects of completing my Ph.D. thesis," said Spann.

Davis is the first researcher to move into the SDSU BioScience Center, where
the connections between inflammation, infection and heart disease are
studied. With more than 33,000 square feet of usable space, the center will
feature three floors of research laboratories, offices and the 100-seat Alan
and Debbie Gold Auditorium for the Life Sciences. The BioScience Center
opened in March 2006.

Heart disease and heart attacks remain one of the United States' leading
health problems. The American Heart Association estimates more than 1.2
million Americans will have their first or a recurrent heart attack this
year. Approximately 479,000 of them will die. In 2006, the Centers for
Disease Control project that heart disease will cost the U.S. economy an
estimated $142.5 billion, including costs incurred due to health care
services, medications and loss of productivity.

The SDSU Heart Institute is sponsored by SDSU's College of Sciences and
College of Health and Human Services and includes approximately 30 faculty
members from a number of health-related disciplines. Its mission is to
promote research and teaching programs relating to heart and cardiovascular
system performance in health and disease, and to increase awareness of
cardiovascular disease and its prevention in the greater San Diego area.

San Diego State University is the oldest and largest higher education
institution in the San Diego region. Since it was founded in 1897, the
university has grown to offer bachelor's degrees in 81 areas, master's
degrees in 72 areas and doctorates in 16 areas. SDSU's nearly 34,000
students participate in an academic curriculum distinguished by direct
contact with faculty and an increasing international emphasis that prepares
them for a global future. For more information, visit http://www.sdsu.edu.

San Diego State University
http://www.sdsu.edu
http://www.medicalnewstoday.com/medicalnews.php?newsid=53599