Baylor team moves closer to solving MD puzzle 
By ERIC BERGER 
Copyright 2001 Houston Chronicle Science Writer 
Scientists have known for a decade what mutated gene causes the most common
type of muscular dystrophy in adults, but until recently they have not fully
understood why the mutation causes the disease. 
Growing evidence, the newest of which will appear today in the journal
Nature Genetics, is giving medical researchers the answer to this "why"
question, which in turn should enhance their ability to devise effective
therapies. 
Baylor College of Medicine researchers will report perhaps the strongest
evidence yet supporting a theory that excess RNA, the molecule that spurs
production of proteins in the body, can effectively clog cells and lead to
muscle weakness and other ailments. 
"The more you know, and the better you understand how things work, the
smarter you'll be when developing drugs," said one of the study's three
authors, Dr. Thomas A. Cooper, a Baylor associate professor of pathology. 
Cooper and his Baylor colleagues, Drs. Rajesh S. Savkur and Anne V. Philips,
are studying patients with myotonic dystrophy whose faulty insulin receptors
do not process enough blood sugar for their muscles to work properly. 
The disease is particularly devastating, Cooper said, because it runs in
families, often getting worse with each subsequent generation. Afflicting
about 30,000 Americans, myotonic dystrophy worsens over time, weakening
muscles, causing cataracts and even mental retardation. 
"It's a very unfair disease to families," he said. 
The mutated gene of those with myotonic dystrophy makes too many copies of
RNA, which, in turn, produce the wrong types of proteins that muscles need
to process blood sugar. 
The genes of healthy people have only a few excess RNA copies, always less
than three dozen. Patients with moderate forms of myotonic dystrophy have
hundreds of copies, and the most severe forms of the disease, sometimes seen
in children, can have thousands of copies. 
Now scientists will know where to look for better treatments -- such as
dissolving the globs of RNA -- and in places they did not consider before. 
"This is a big step forward," said Dr. Sharon Hesterlee, director of
research development for the Tucson, Ariz.-based Muscular Dystrophy
Association, which helped fund the study. "The pieces of this disease's
puzzle are really beginning to fall into place. It gives us a much better
idea of what to target for therapies." 
Hesterlee said Cooper's work is consistent with research published in
another journal last month also supporting the theory that RNA blockages are
causing most of the symptoms of myotonic dystrophy. 
Cooper said the next step for researchers, having identified RNA as the
culprit, is to understand precisely why the excess RNA is botching efforts
by the body's cells to produce the correct proteins allowing muscles to act
as they should. That will provide more effective, targeted therapies, he
said.