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The
Father of Invention
Isner,
a cardiologist at Tufts Medical School and New England Medical
Center was seeing too many patients he didn't know how to
help.
"They were trying to inhibit vascular growth," says
Isner. "It occurred to us that we should encourage it."
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"These
were generally very end-stage patients and we had very little
to offer these people," says Isner of his patients who were
too sick to be eligible for transplant or angioplasty.
"One
way to help them was to try to do the reverse of what Judah
Folkman's lab was doing," Isner explains. "They were trying
to inhibit vascular growth and it occurred to us that we should
encourage it."
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A
balloon coated with the vessel-growing gene is inserted
into the patient's artery. |
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Isner's unique approach was to introduce a gene into ailing
blood vessel cells that would stimulate the growth of new
vessels around a blockage. Unable to persuade any biotech
company to produce mass quantities of a virus vector for this
growth stimulating gene, called VEGF, Isner ran trials with
"naked DNA," inserting millions of copies of the gene directly
into the cells in blood vessel walls.
"The
approach we take turned out not to be useful in treating heritable
disease," says Isner. "But our methods are suitable for very
localized, relatively transient expression. We only need the
gene to work for two to four weeks."
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This
gene therapy candidate shows dangerously slow blood flow
to the lower leg. |
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Inser's
results have so far been very encouraging. The
minimally invasive procedure, with seemingly no side affects
nor need for immuno-suppressing drugs as with a transplant
operation, looked extremely promising.
"That's
one of the attractive features of this method- it's simplicity,"
says Isner. "While one cannot be cavalier about the dangers,
nevertheless there are not yet any red flags and there are
some very intriguing hints of efficacy."
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