For the first time cured brain degeneration by ... HIV virus

For the first time in history, doctors have done what seemed to be impossible to treat fatal degenerative brain disease with genetic modification therapy. More surprisingly, the virus is the key to this success.

What do I have to do to save my child?

In 2000, Dr. Amber Salzman's nephew, from the Board of Directors of GlaxoSmithKline Pharmaceutical Group, was diagnosed with ALD , a disease she only heard in the movie "Lorenzo's Oil" (The miracle drug of Lorenzo). .

'It is a smart, lovely child. Suddenly, she collapsed in front of me and completely lost all her abilities , 'Salzman said.

She also has a 1-year-old son who is diagnosed with a genetic mutation like her grandson. She looked at Lorenzo's Oil and studied the strict diet but didn't work.

Dr. Salzman met Dr. Tachi Yamada, who led the research and development team at Glaxo and said: 'Before the bomb explodes in my son and other boys, what should I do to save them? ? '

Dr. Yamada told her that the best way is gene therapy , but it has never been tested against a disease like ALD.

In fact, gene therapy is often not preferred when patients under 18 years of age have had many previous deaths such as Jesse Gelsinger: died in an experimental treatment. Then, in 2003, four of the nine children treated for leukemia were also killed.

Without hesitation, Dr. Salzman, with the help of his sister, Rachel, and other scientists, gathered researchers around the world, figuring out how to use a virus to bind an ALD gene. Good to the boys' cells. After a period of research, the HIV virus has been disabled to become the best choice to perform this "task" safely.

Scientists are also a little concerned about the use of HIV virus in treatment. But Dr. Salzman said: "I will not refuse to try this plan. I can only be cautious about the objections."

Despite all the protests, Dr. Amber Salzman called on researchers to find genetic modification methods to treat patients with this rare disease.(Photo: New York Times) .

Unexpected effect from gene modification therapy

ALD is usually detected in boys with a ratio of 1 / 20,000, the average of the first symptoms of the disease usually occurs when the baby is 7 years old. The only treatment is a bone marrow transplant if it is possible to find a compatible donor or transplant from an umbilical cord if kept at birth.

But such transplants are very difficult and dangerous, with mortality rates of up to 20% and some survivors who are also disabled for life.

After a period of lobbying, Dr. Salzman and his colleagues were allowed to conduct a small study in France, in which they used a form of HIV that was disabled to be put into the body.

The study was based on 17 boys, from 4 to 13 years old. After two years, 15 babies returned to normal life and there were no obvious symptoms of the disease; 1 baby died because the disease progressed so quickly, surpassing the ability of treatment; A baby would withdraw from the experiment to perform a bone marrow transplant but also died during surgery.

Dr. Jim Wilson, director of gene therapy programs at the University of Pennsylvania's Perelman School of Medicine, who is not involved in the study, said: "It seems to me to be effective."

Dr. Theodore Friedmann, a pioneer in gene therapy at the University of California San Diego School of Medicine, said the study opens new avenues for using gene therapy to treat brain disease.

"Many people think that the central nervous system is intractable and inaccessible. This study proves they are wrong," he said.

The idea behind this treatment is similar to: taking bone marrow stem cells from a boy with an ALD mutation. Insert a good gene into the cells and then transfer them back into the bone marrow. Wait about a year while stem cells with good genes multiply in the bone marrow. Eventually, they move into the brain, where they slowly turn into nerve cells to support cells that surround neurons and protect neurons. These good genes will replace mutant genes in brain cells, preventing brain decline if possible.

David A. Williams, scientific director at Children's Hospital Boston and a major researcher, said the procedure also explains why bone marrow transplantation is effective. New bone marrow cells, from a healthy donor, provide good genes for cells in the recipient and eventually become glial cells.

Prompt treatment before "cannot be cured"

According to the researchers, any treatment must be done early, before the symptoms are clear. Because during the treatment period, the brains of children who have obvious symptoms may become so bad that they cannot be cured.

Brandon Rojas, 10 years old, and mother, Liliana in their house in Dover Plains, New York.(Photo: New York Times).

For Paul Rojas, who lives in Dover Plains, New York, the study of gene therapy has saved the life of his son. He had never heard of the disease until his son Brandon was 7 years old. At that time, Brandon started drooling, lost his ability to concentrate and paralyzed one leg. He was shocked when he heard the diagnosis. Brandon showed symptoms, so it was too late to transplant bone marrow.

Brandon's doctor informed Rojas and his wife, Liliana, that their son had suffered from an incurable disease. Rojas immediately reported that his second child, Brian, 4, went on a test and unfortunately the boy also had the genetic mutation.

While Brian (blue shirt) had no sign of ALD, Brandon, now 10 years old, could not speak, walk or eat.(Photo: New York Times).

The Rojas family could not find a compatible donor to conduct a bone marrow transplant . But then, he learned about the trial of genetic modification therapy so he signed up for Brian to participate in the experiment. Brian is now 7 and doesn't have any signs of illness. But Brian and Brandon's brother - now 10 years old, cannot speak, walk or eat at all. Brandon must maintain life through a feeding tube.

Rojas said;'Brian missed his days with Brandon, Brandon was his idol.'

For Dr. Salzman, the results came too late. She had to treat her son before he got sick. But luckily, her son had a successful cord transplant. However, her grandson had complications and had to use a wheelchair.

Brandon was 7 years old when she was diagnosed with ALD.(Photo: New York Times).

Cost will not be cheap?

The success of this small pilot study was enough to inspire the establishment of a company. Bluebird Bio has funded a larger study in the hope that it could be put into practice soon.

The company has now expanded its research to eight more boys, in parallel with this study, which is a separate study for bone marrow transplant boys to compare the results.

The results of this new study also increase the common interest of new gene therapies and biotechnology therapies: How much does this treatment cost?

Bluebird Bio does not answer this question. (Usually companies do not announce prices until their drugs are approved.)

Dr. David A. Williams, scientific director at Children's Hospital Boston and a key researcher of this study, predicts the cost will be comparable to bone marrow transplantation (about hundreds of thousands of dollars).

As for Dr. Friedmann, he was not caught up in such arguments. Research before these products are marketed is often funded by the federal government or from private funds.

He said: 'This is a therapy and it's crazy to get too high prices.'

Although there are still many issues that are being debated, it is undeniable that genetic modification therapy has brought many hopes of finding life for desperate patients.

Adrenoleukodystrophy (ALD) is a rare disorder in children, caused by a genetic mutation.

ALD causes the nerve cells in the brain to die slowly, and only a few years later, the patient loses the ability to speak or move.

Most children have to live a plant life, unable to hear, see, think or eat without supportive catheters. Patients often die within five years of being diagnosed.