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                        JeffNEWS, February 21, 1995
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Jefferson Cardiologists Lead Research and World's First Clinical Trials 
Exploring Gene Therapy for Heart Patients
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A bold idea conceived by two Jefferson cardiologists four years ago may 
offer new hope for heart disease patients the world over. 

For years, doctors knew that clogged heart arteries in many patients 
frequently reclose within months of being cleared by balloon angioplasty - 
a procedure where tiny balloons are inserted in the clogged arteries to 
clear them. When their heart arteries reclose - called "restenosis" - many 
patients repeat the expensive and invasive balloon angioplasty. 

When Andrew Zalewski, MD, research director and interventional 
cardiologist, division of cardiology, and associate professor of medicine, 
Jefferson Medical College, and Yi Shi, MD, PhD, assistant research 
director, cardiology, and research assistant professor of medicine, 
Jefferson Medical College, studied adverse after effects of balloon 
angioplasty on patients, they found it likely that 40 percent of the 
500,000 patients who received balloon angioplasty in 1994 will have 
restenosis within six months. 

Blood vessels' own healing response causes restenosis
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They determined that a major cause of restenosis is the blood vessels' 
own healing response to the angioplasty intervention, which removes plaque 
lining the clogged vessel walls. The vessels' natural healing response is 
to produce scar tissue on the vessel walls. This build-up of soft muscle 
scar tissue can cause restenosis, Dr. Zalewski explains. 	

Rather than reclearing the artery walls by follow-up angioplasty 
procedures, doctors are exploring ways to keep restenosis from happening in 
the first place. Drs. Zalewski and Shi came up with the idea that 
restenosis might be avoided if the gene stimulating the growth of scar 
tissue cells in the affected arteries was "blocked." 

The idea was daring for its time. That's because the biotechnology of 
healing a disease by "blocking" the gene that helps cause it - called 
"antisense" technology - was so new. Only within recent months has evidence 
began appearing that the new antisense technology - always theoretically 
sound - might actually work to heal or, better, prevent disease.

Jefferson antisense research reaches clinical trials
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Today the Jefferson cardiologists' work is among only a handful of 
antisense research projects to reach the critical phase of clinical trials 
involving patients. In fact, it's the first clinical trial in the world to 
use antisense technology in cardiac patients.

Since November, about 30 patients undergoing angioplasty have also been 
receiving antisense dosages in clinical trials conducted at three sites in 
Buenos Aires, Argentina, under the direction of a long-time colleague of 
Dr. Zalewski, Dr. Fernando Roque. The purpose of this Phase I clinical 
trial, whose data is being analyzed at Jefferson, is to determine the 
safety of the antisense. 

Domestic clinical trials involving 2,000 patients will begin this fall, 
with Jefferson serving as the lead site in conjunction with several other 
leading medical centers in the United States.

Dr. Zalewski expects the domestic clinical trials to last about three 
years, or through 1998. If their outcome is successful, it will mean gene 
therapy for restenosis will be available to thousands of heart patients 
every year, not only in the United States but all over the world.

Dr. Zalewski sums up by saying, "It is especially satisfying and fitting 
that all vital stages of this important project occurred at Jefferson. The 
idea was first conceived at Jefferson, then it was tested in preclinical 
research at Jefferson, and now, based on these findings, clinical research 
is being directed by Jefferson and later this year will be based at 
Jefferson.


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Information provided by:  Editor, JeffNEWS
                          (215) 955-6204
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