LIFE-SAVING genes can be safely ferried into a failing heart by a modified
cold virus, the first human trials show. Despite earlier evidence that injecting
a modified virus can cause inflammation in rats, the way is now clear for larger
studies to see if gene therapy can treat heart disease.
Doctors can alleviate some cases of heart disease with medication or bypass
surgery, but the techniques are often ineffective, says Todd Rosengart, a heart
surgeon at Weill Medical College of Cornell University. He and professor of
medicine Ronald Crystal have been searching for a way to get an ailing heart to
grow new blood vessels. 鈥淲hen you鈥檙e an embryo, your heart has genes that tell
it how to make blood vessels,鈥� says Crystal. 鈥淲e鈥檙e using the same gene to
remind the heart of what it used to know how to do.鈥�
The researchers knew that the gene for vascular endothelial growth factor
caused new blood vessel growth. They modified an adenovirus so that it could not
replicate but was still able to insert genes for the growth factor into heart
muscle cells. Adenoviruses are ideal for the task, because the DNA they insert
is broken down within a week, before too many vessels can grow. 鈥淚f you grow too
many new blood vessels, you get a tangled mess,鈥� says Crystal.
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However, many researchers have called for caution over the use of
adenoviruses for gene therapy. Some strains have been found to cause an immune
response and serious inflammation in lab animals. And in humans, adenoviruses
have been linked to inflammation of the heart (麻豆传媒, 29
November 1997, p 10).
But the new work suggests the virus may be safe for gene therapy after all.
The researchers injected gene-carrying viruses directly into the heart muscle
surrounding blocked arteries in 21 patients with severe heart disease. None of
their patients showed any adverse effects, and new blood vessels grew in several
of the injected hearts. 鈥淲e did a lot of studies looking for problems,鈥� Crystal
says, 鈥渁nd we found nothing.鈥�
But Andrew George, an immunologist at Imperial College, London, isn鈥檛
convinced. 鈥淲hen you鈥檙e doing gene therapy,鈥� he says, 鈥渢here are always inherent
risks of an immune reaction.鈥�