Gene therapy starting to work

Gina Miller (
Sat, 12 Jun 1999 14:17:52 -0700

Saturday June 12 12:23 AM ET

Gene Therapy Finally Starting To Work, Doctors Say By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - Gene therapy, which for years has produced disappointment after disappointment, may be on the verge of yielding successes, scientists said Thursday.

The scientists said they finally were developing ways to get genes into the body so they stay there and keep working -- one of the biggest stumbling blocks so far.

And they also have tempered their expectations, with gene therapy being just that -- therapy -- rather than a hoped-for cure for many genetic diseases.

``We can use it in the treatment of cancer, inducing an immune response to
infection or cancer, the sprouting of blood vessels, all those sorts of things,'' Dr. Jim Wilson, president of the American Society of Gene Therapy, said in an interview.

``It's like a drug delivery vehicle where the drugs are therapeutic
proteins,'' Wilson added.

The society is holding its annual meeting in Washington.

The original idea behind gene therapy was to replace faulty genes that cause diseases such as cystic fibrosis, an inherited disease caused by mutations in one gene.

But attempts to replace this gene in patients did not work well. Sometimes their cells did not take up the gene, or it worked for only a short time.

This might have been due to the vectors, the methods used to carry the new genes into the cells.

Commonly used vectors include viruses known as adenoviruses, best known for causing the common cold. But they caused inflammation and other immune responses that attacked the genes and shortened their useful lives.

Now, viruses known as adeno-associated viruses (AAV) are being tested. They do not themselves cause infection but seem to be very good at injecting the genes right where they need to be in a cell, so that they last.

``Tested in animals it looks spectacular for stable expression,'' Wilson
said. ``We can essentially cure disease in animals.''

The genes keep expressing -- directing the cells to produce the right proteins -- for as long as two years in dogs and rhesus monkeys, Wilson said.

Clinical trials in human beings are just starting, and the first results will be reported next year, Wilson said.

With success comes new problems, however.

``You have to consider the power and the danger of a gene that's just
sitting there,'' Wilson added. ``What if you get too much?''

Dr. Michael Lotze of the University of Pittsburgh found out. He was testing a gene for interleukin-18, one of the body's natural immune system signalers that he hopes eventually to use to treat cancer.

``These are molecules that we thought would be kinder and gentler than the
drugs we apply,'' Lotze told a news conference.

But in fact, they were highly toxic.

``It makes all the tumors go away but all the animals die, too,'' Lotze

The way to control this is by using several genes, one of which controls the others and is turned on and off by an outside drug.

``I call it a molecular rheostat. You can dial it up and dial it down,''
Wilson said.

A team at Cambridge, Massachusetts-based Ariad Pharmaceuticals Inc. (Nasdaq:ARIA - news) has accomplished this with the genes for erythropoietin, which is used to treat anemia, for human growth factor and for insulin, used to treat diabetics.

Patients are given genes called transcription factors. They are only turned on when a patient takes a certain drug, often an antibiotic, allowing the doctors carefully to control how much of a protein is produced.

Wilson said gene therapy could help drug companies develop many more products much faster. Currently, they must identify a target -- for example, a gene controlling inflammatory chemicals in the body that are overproduced in rheumatoid arthritis.

Then they must produce in the laboratory the same protein that the gene expresses, which is not an easy task. They have to produce it in large enough amounts to test. Then they have to develop a drug that activates or blocks this protein, manufacture that drug and go through years of clinical testing.

``Gene therapy could short-circuit a lot of that,'' Wilson said. ``You may
never have to purify a protein or manufacture a small molecule drug. You just have to make the vector and get it into the patient. Why bother making it? You can just let the cell do it.''

Gina "Nanogirl" Miller
Nanotechnology Industries
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"Nanotechnology: solutions for the future."