AIDS STUDY OFFERS HOPE : TEEN IN RUNNING FOR EXPERIMENT IN GENE MANIPULATION.

Byline: Keith Stone Daily News Staff Writer

Fourteen-year-old Cameron Siemers knows that a unique AIDS experiment set to begin in Los Angeles may be his last, best chance at life.

If only he could get into the study, then the doctors would try to give him powerful, new immunity by tinkering with his genes.

``But I don't want to be in it,'' the teen-ager said, ``if there is someone who is sicker than me.''

His parents frowned.

``Let's be a little less generous,'' said his father, Ken Siemers. ``Let's fight for that. It is worth fighting for.''

There is no guarantee that Cameron will be chosen for one of five spots in the experiment, the first of its kind to involve children. Selection for the study, expected to begin in the fall, will be based on the children's health and other medical criteria.

And even if Dr. Donald Kohn and Dr. Joseph Church are correct and this new gene therapy halts the progress of HIV, the virus that causes AIDS, the first experiment itself is not expected to prolong lives because it involves genes in only a small quantity of cells. Genes contain DNA, the road map for every cell's operation.

``This is step one,'' said Kohn, director of the Gene Therapy Program at Childrens Hospital of Los Angeles. ``It is very unlikely that any of these first trials are going to cure anyone.''

``I stake my career on the belief that one day we will be treating diseases by gene therapy,'' he said, ``but right now we are at the very beginning.''

Any measure of hope is hope enough for Linda and Ken Siemers, parents of the Anaheim teen-ager.

Since their son, a hemophiliac, contracted HIV through a blood transfusion, his immune system has collapsed entirely, leaving him open to even the most routine infections. Worse yet, the freckle-faced baseball player is developing resistance to one anti-AIDS drug after another and soon none will work at all.

``We will just keep playing the roulette wheel hopefully, until this study comes up,'' said Linda Siemers.

Kohn has proved in laboratory tests that by genetically altering the body's blood-producing cells, the cells can protect themselves from the onslaught of HIV. If that works in humans, then the progeny of those resistant cells might themselves be armored to the elusive, killer virus.

Now the Food and Drug Administration is working with Kohn in anticipation of inserting these manipulated genes into children between 7 and 18 years old. Testing on humans could begin by the fall.

Dr. Phil Noguchi, director of the FDA Office of Cellular and Gene Therapies, says he expects that Kohn's study will be approved as part of the government's growing focus on gene therapy.

``We see this as a beginning of a long road ahead and, we hope, a fruitful road ahead,'' Noguchi said.

With each gene therapy experiment since the first in 1990, researchers have learned more about how to cure stubborn diseases by dissecting and modifying genes.

Still, the results have been mixed.

Kohn won worldwide attention in May 1993 when he was the first to use gene therapy on babies born without immune systems. Three years later, the genes have taken hold and appear to be helping restore at least some of the children's immunity.

But last year researchers reported that gene therapy experiments had failed to turn back cases of cystic fibrosis and Duchenne muscular dystrophy.

Now Kohn proposes enlisting genes in an experiment that government scientists say is fundamentally unique.

``While previous studies have focused on adults infected with HIV, this is the first protocol to focus on children with HIV,'' said Dr. Nelson Wivel, director of the National Institutes of Health Office of Recombinant DNA Activities.

``There may be differences in the way this infection plays out in adults vs. pediatric populations,'' Wivel said. ``It will be very important information derived from this particular study.''

Kohn is circumspect about success.

``Gene therapy is speculative,'' he said. ``Although we can get the cells to do what we want in the laboratory, it's not known what it will do in a patient.''

The Siemers try desperately to temper their enthusiasm with Kohn's and Church's words of caution, but they find it increasingly hard as they watch Cameron grow and enjoy life.

He plays street hockey. He got his first hit in Pony baseball. He is discovering girls. He dreams of going to college. But every day he takes 15 pills and needs bimonthly infusions of gamma globulin to boost his immunity.

``This will drive you crazy if you think about it every day,'' said Linda Siemers, a rapid-speaking 35-year-old registered nurse.

``I always have to restrain her,'' said Ken Siemers, a 34-year-old teddy bear salesman who speaks softly with carefully chosen words. ``I swear it makes it worse if you dwell on it.''

To help Kohn assemble enough information for his application to the FDA, Cameron and other children endured the extraction of bone marrow a year ago, a painful process with an auger-like needle.

For participating, Cameron received $100, which he spent on Super Nintendo games. But the teen-ager said the games meant little: He wants to help cure AIDS.

``I am glad I never saw the needle. My mom says it was real big,'' he said, but quickly added: ``If you are going to go on a study, and you get a little pain - it is nothing.''

The Siemerses said they allowed doctors to take Cameron's marrow because they thought it would boost his chances of being included in the experiment. At the same time, they say they knew from the consent form that the doctors could make no promises.

Kohn and Church say they understand the Siemerses' dilemma.

``It is a difficult situation,'' said Kohn, who has two children himself. ``That is why I don't know the patients because I am a sucker; I meet a kid, and I would want to help him too.''

Church selected Cameron and the other children from among the 120 he treats for HIV infections at any given time. More than half of the youngsters who donated have since died.

To qualify for testing in humans, Kohn and Church will want to know whether Cameron's body, in the past year since they last took marrow, can still produce enough stem cells. These cells give birth to red and white blood cells, key among them the virus-killing T cells.

So far, despite Cameron's failed immune system, he has had no major illnesses.

``He is a good candidate,'' said Church, who directs the AIDS center at Childrens Hospital. ``We would certainly offer him a spot, at least as far as getting the initial bone marrow (extraction) done.''

The procedure works like this:

Stem cells are extracted from marrow, injected with an ``RRE decoy'' gene, using a gutted mouse virus as an ersatz hypodermic needle. The altered cells are then inserted back into the body.

The new gene is designed to confuse the HIV and capture an essential protein, thereby blocking the virus from reproducing.

``If it works,'' Kohn said, ``then the stem cell now has a new gene and every time it divides, both daughter cells get this new gene. So if the stem cells go off to produce hundreds of millions of T cells, every one of them should have that protective gene.''

It is unlikely that these newly armored T cells would kill all of the HIV and rebuild the immune system entirely, Kohn said. To achieve that, all unprotected stem cells would have to be eliminated through radiation and chemotherapy and then replaced with the genetically charged cells.

``That is a bold step,'' Kohn said. The Siemerses hope it is not a step too late for Cameron. He said he tries not to think about his illness, but late at night the virus haunts him.

``A lot of times I think: I am just going to get sick and go to the hospital,'' he said. ``I just don't think about it - what happens when you die. I am not sure. My grandma says she's sure. She says you go to heaven. That is what she says - and I have to trust her.''

CAPTION(S):

2 Photos

PHOTO (1 -- color) Cameron Siemers, 14, hopes to be chos en for an experimental AIDS therapy for children.

David Sprague/Daily News

(2 -- color) Drs. Donald Kohn, left, and Joseph Church are pioneering gene therapy to treat AIDS at Childrens Hospital of Los Angeles.

Michael Owen Baker/Daily News