Gene Therapy

When Gustavo D. Aguirre peered into the eyes of his small fluffy patient, a dog called a Coton de Tulear, he was surprised to see a small blob beneath the retina, almost like an egg yolk. Within a year, the blob had degenerated so it looked like scrambled eggs. It reminded Aguirre, a professor at the University of Pennsylvania School of Veterinary Medicine, of the symptoms in a form of human blindness called Best disease. Could the dog have a canine version of the same thing?

Perhaps nothing has become as synonymous with futuristic medicine as gene therapy. But, as brought home by the recent death of a young research subject at the University of Pennsylvania, the dangers are still not well understood. The investigation into the death of 18-year-old Jesse Gelsinger revealed that it probably wasn't the genes he was getting that caused his death. Rather it appears that the death was the result of the delivery vehicle for those genes - in this case a virus modified so it wouldn't cause an infection.

In the mountains of Peru, in the remote village of Paran, 50 of the 400 residents are blind. It has been like this for at least five generations. Families have come to expect and accept that some of their children are likely to live out their lives in darkness. But on June 13, an e-mail signaling hope for the villagers arrived in Gustavo Aguirre's tiny, windowless office at the University of Pennsylvania School of Veterinary Medicine. A Peruvian researcher who had taken DNA samples from the villagers had just received the results of a genetic test.

For a quarter of a century, gene therapy has been stymied, largely because the patient's immune system attacks the treatment as a suspected rogue - or because it actually does turn rogue. Now, University of Pennsylvania researchers have convincingly shown that they can overcome these formidable obstacles. Cells that were genetically modified to fight HIV have persisted for up to 11 years - and counting - without bad side effects in 41 patients. In two other patients, the modified cells were safe but not as durable, according to the Penn study, published last week in Science Translational Medicine.

We have entered a new era of super-hyped science, personal glory seeking, and overnight millionaires from biotech speculation - the sort of atmosphere that leads to the "snake-oil" overselling of medical treatments. Now comes a disturbing indictment of the most publicized and promising field of medical science, gene therapy. That's the hopeful term for treating cancer, cystic fibrosis and other diseases by replacing defective or missing genes. It comes from a committee of physicians and scientists appointed by the National Institutes of Health (NIH)

In a development that may overcome a major stumbling block to gene therapy, scientists at the University of Pennsylvania Medical Center have figured out how to turn the treatment gene on and off in mice and monkeys. Such control over therapy is crucial. Too much medicine can be as dangerous as the disease itself. "Ideally what you want to be able to do is to turn the gene on when you want to and switch it off when you don't want it," said French Anderson, director of the gene-therapy laboratories at the University of Southern California.

In another attempt to reopen its stalled gene-therapy clinical trials, the University of Pennsylvania again defended its conduct of a trial that caused the death of an Arizona teenager last year. In response to a March 3 warning letter from the federal Food and Drug Administration that detailed a number of problems with the trial, Penn and its Institute for Human Gene Therapy yesterday said numerous measures were underway to prevent the problems from reoccurring. In a 14-page letter to the FDA, the institute, led by scientist James M. Wilson, said it had contracted with an independent company, Parexel International Corp.

In a feat that is renewing hopes for conquering AIDS, researchers have genetically engineered patients' vital immune cells to make them resistant to HIV infection. To confer this invulnerability, scientists took the immune cells from HIV-positive patients' own blood, then snipped out a single gene - the first time such a precise alteration has been achieved on a meaningful scale. When put back in the patient, the cells no longer make a receptor that HIV needs to enter the cell, effectively blocking the virus.

Scientists have developed a genetic technique that may make it possible to treat people suffering from cystic fibrosis and other deadly lung diseases by spraying aerosols into their throats. The treatment represents a dramatic advance in the exploding field of gene therapy - the altering of genetic material in a patient's cells. In a study being published today in the journal Science, researchers said they used the treatment to transfer a human gene into the lung cells of rats.

Donald appeared much more relaxed than the researchers watching from the edges of the operating room as nurses and anesthesiologists readied him for surgery. He was about to undergo a revolutionary cancer treatment, and the scientists had reason to be tense. They were trying a new form of gene therapy and didn't know how dangerous it was or whether it would work. Donald, 64, was a retired asbestos worker with less than two years to live. He was being killed by mesothelioma, a rare cancer that attacks the membranes covering the lungs and the opposing chest wall.

When Gustavo D. Aguirre peered into the eyes of his small fluffy patient, a dog called a Coton de Tulear, he was surprised to see a small blob beneath the retina, almost like an egg yolk. Within a year, the blob had degenerated so it looked like scrambled eggs. It reminded Aguirre, a professor at the University of Pennsylvania School of Veterinary Medicine, of the symptoms in a form of human blindness called Best disease. Could the dog have a canine version of the same thing?

University of Pennsylvania researcher Carl H. June has been selected to receive the 2012 Philadelphia Award for "his extraordinary advancements in gene therapy aimed at treating HIV and cancer. " June and his team recently reported that of the first 12 patients treated with the experimental therapy, nine - including two children - had complete or partial remissions from advanced intractable leukemia. Two adults remain cancer-free 21/2 years after treatment. The annual award, which carries a $25,000 honorarium, was created by Ladies' Home Journal editor Edward Bok in 1921 to honor a local person whose work advanced "the best and largest interest" of the greater Philadelphia community.

Aaron and Christal Walker live in dread that their daughter will get sick, and in dread that she won't. Six days ago, Avrey Walker, 9, of Redmond, Ore., became the seventh child to receive an experimental gene therapy for leukemia at Children's Hospital of Philadelphia. She will soon suffer several days of fevers, nausea, headaches, maybe worse - if the therapy works as it should, marshalling her immune T cells to fight her cancer. Four of the first five children to undergo treatment and get lab results are cancer-free, according to their families and doctors.

Nora Situm, the 5-year-old Croatian girl whose homeland raised money for her to seek experimental leukemia therapy at Children's Hospital of Philadelphia, died early Wednesday while the tailor-made treatment was still being produced. "We are very sorry for the loss of Nora Situm, and express our deepest sympathies to her parents, family, and many friends and supporters in Croatia," the hospital said in a statement. "During the time Nora was in our care, we were in awe of the tremendous courage and spirit displayed by her and her parents.

Nora Situm, the 5-year-old Croatian girl whose homeland raised money for her to seek experimental leukemia therapy at Children's Hospital of Philadelphia, died early Wednesday while the tailor-made treatment was still being produced. "We are very sorry for the loss of Nora Situm, and express our deepest sympathies to her parents, family, and many friends and supporters in Croatia," the hospital said in a statement. "During the time Nora was in our care we were in awe of the tremendous courage and spirit displayed by her and her parents.

Still groggy from painkillers, Maddie Major, 7, clutched her stuffed Pooh Bear and laid her head on her father's shoulder as he carried her to the hospital cafeteria. Maddie, dad Tim, mom Robyn, and big sister Candace spent that February morning at Children's Hospital of Philadelphia, where a doctor extracted samples of the child's spinal fluid and bone marrow. In a few days, the biopsies would reveal whether Maddie's leukemia had been wiped out by an experimental gene therapy made from her own white blood cells - crucial disease fighters called T cells.

Two months ago, Children's Hospital of Philadelphia made international headlines for using an experimental gene therapy to save the life of a Pennsylvania girl who was dying of leukemia. On Wednesday, the hospital made international headlines - and was denounced on Facebook as "cruel" and "heartless," as being "greedy monsters" and worse - for appearing to tack on hundreds of thousands of dollars to the original price of treating a Croatian child, Nora Situm, 5, with the same breakthrough therapy.

The perception that Children's Hospital of Philadelphia jacked up the price of treating a Croatian child is "a big misunderstanding," the child's mother said on the hospital's Facebook page, pleading with Croatian supporters "not to write any more bad comment on the hospital pages. " Dana Atanasovka Situm, who is taking her 5-year-old daughter Nora Situm to Children's for a last-ditch experimental therapy for leukemia, apologized for the misunderstanding and blamed the hurry and confusion of the past few days.

Two months ago, Children's Hospital of Philadelphia made international headlines for using an experimental gene therapy to save the life of a Pennsylvania girl who was dying of leukemia. On Wednesday, the hospital made international headlines - and was denounced on Facebook as "cruel" "heartless," "greedy monsters" and worse - for appearing to tack on hundreds of thousands of dollars to the original price of treating a Croatian child, Nora Situm, 5, with the same breakthrough therapy.