And after the "Berlin patient" … what?



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These days, Mr. Gero Hütter prepares his luggage to go to San Francisco. Last Wednesday, the same day that German magazine Stern published the story of Timothy Ray Brown and a scientist from paper confirmed that this 44-year-old publicist had become the first human to eradicate HIV from his body, the German doctor received a call from a colleague in Frankfurt: "I have another patient," he said. It's a 43-year-old man who lives in the American city and who, like Timothy, is a carrier of the AIDS virus and is suffering from leukemia, a type of cancer that involves the uncontrolled proliferation of white blood cells, cells charge. to protect the body.

Since 2008, he has been trying to replicate the conditions that led him to experiment with stem cell transplantation as a treatment for AIDS. It was not easy. First, look for patients with both diseases (leukemia and AIDS) and look for the appropriate donor. Then let the intervention work. Some patients died before even trying, in others, there was simply no good results. But Dr. Hütter is hopeful: "He had never thought of this possibility until the day Timothy arrived at the hospital, and then the idea came to my mind. talking about a cure for AIDS was just triggering laughter, which you labeled as crazy.Now, after this case, the medical world considers that healing is possible, "says Hütter in a telephone conversation with La Tercera during his consultation in the German city of Mannheim, south of Berlin.

It was four years ago. At that time, the doctor was working at the La Charité University Clinic in Berlin. Until then, Ray Brown – an American living in Germany – had been living with HIV since 1995, had been treated with drugs, but in 2006 he was diagnosed with leukemia that had made him near death, after the failure of chemotherapy. It was then that Hütter had the idea: the only possibility was a stem cell transplant, which would completely renew his immune system. With the help of radiation, doctors destroy the patient's bone marrow and replace it with healthy cells from an anonymous donor. But this donor had to have a particular characteristic: to be carrying the genetic mutation that prevents lymphocytes from containing the CCR5 receptor, one of the doors that the virus uses to penetrate the cells and, from there, to multiply. It was a gamble, but logic told him that if the new cells of Timothy's immune system were resistant to HIV, the virus would eventually die.

As a hematologist, his experience with AIDS patients was lean. But he remembered what he had read as a student on the CCR5 and began looking for research that had experienced the same thing.

He found nothing. "I thought there should be an error in the way I thought about the problem – he did not understand how it had been thought before, if it sounded very simple and logical," he recalls. After several genetic badyzes, they found the donor. And although the recovery has been long and complex, Timothy has no trace of the virus in his body for four years now.

"I think there will be good news in five or ten years, in the 80s it was thought that the treatment would be reached in five years and that thirty years have pbaded, but today we can see that it will be over. While gene therapy works, we have what it takes to find a cure, but we still do not know how to use it, "says the doctor.

Current research

Transforming the technique used by Hütter into a therapy that could be used mbadively is impractical.It is completely impossible to find donors carrying the mutation and submit carriers of HIV to radiotherapy to destroy their Immune system then graft them. "From a practical point of view, it has no mbadive utility. It can not be repeated ten or hundreds of times in different patients. But it's a biological revelation, "says Dr. Pablo Vial, a specialist in infectious diseases and dean of the Faculty of Medicine of the Universidad del Desarrollo

The biological revelation evoked by Dr. Vial refers specifically to the possibility to use CCR5 as a brake on HIV and thus to find a cure

The results of Hütter – known in advance in 2008 – aroused the curiosity of several research groups around the world attention in CCR5 One of these is headed by Dr. Karl-Heinz Krause, of the Experimental Cell Therapy Laboratory of the University Hospital of Geneva (HUG).

During a conversation with La Tercera, Krause explained that his goal was to go even further.German Research. "From a technical point of view, bone marrow transplantation does not seem realistic. We are trying to find ways to work with the patient's own marrow, which is effective, "he said. The idea, he explains, is to extract some of the bone marrow, genetically modify it in the laboratory, block the expression of CCR5 and reinsert it into the patient, into the goal of multiplying the generation of immunized lymphocytes against HIV. It's a bit like putting a padlock on the door.

Between February and March, they will experiment with mice to which a modified human immune system not expressing CCR5 has been adopted. After that, they will be infected with HIV to see if they are resistant. "We are working with conventional genetic engineering and hope to publish these results by the end of next year," Krause said.

Renier Myburgh, a biologist and doctor of gene therapy working for the team, explained the procedure: "We imitate the natural processes with which the body regulates its genes.We locate the gene that produces this receptor, but let's insert an artificial genetic sequence created by myself, that will replicate the interference of ribonucleic acid (RNA) and block CCR5. "All this, without the need of a donor and with a similar performance to that of a vaccine, so that they do not believe that there are side effects in the treated patients.

The City of Hope Research Hospital in Los Angeles is doing similar work. , United States. There, a team of scientists, led by oncologist David DiGiusto, is also interested in the idea of ​​autologous cells. His work was published in June of this year by Science Translational Medicine. Four HIV carriers and lymphoma patients (a common cancer in HIV-positive patients) were autotransplanted with genetically engineered and cultured cells, to extend the effect of the technique before reimplantarlas.

Three were genetic modifications obtained in the laboratory: they introduced a molecule that inhibits the replication capacity of HIV, another that slows the capacity of the TAT protein (which also promotes the reproduction of the virus) and another molecule that Ribonucleic acid (RNA) which inhibits the production of the CCR5 receptor. In this way, not only hides the door of HIV entry, but also attacks their ability to reproduce. After 11 days, the new cells would normally reproduce in the patients' body, but after two years, their levels had dropped. With these results and as the researchers themselves admit, the next step is to ensure that the modified cells are not destroyed by the patient's immune system.

Calm and Moderation

According to the Laboratory Cell Therapy at the Geneva Hospital, yes, Krause is watching the progress of his team calmly. "In French, it is said that a swallow does not make spring and I think that's the way to see it," he says. Although most specialists – like Krause – insist on being cautious, the environment is optimistic. "The history of the Berlin patient is proof that healing is possible and worthwhile, which opens the door to gene therapy and to others that do not pose as much risk to the patient," ] The Tercera Michael Saag, AIDS expert at the University of Alabama and former president of the medical badociation. Ron Swanstrom, professor of microbiology and immunology at the University of North Carolina and one of the scientists involved in decoding the HIV genome: "Many scientists are researching, looking for drugs that activate the genes that are There's a lot of science we're working on. "There can be a functional cure in about 10 or 20 years more."


The Story of a Defective Gene [19659002] The story of this medical success begins well before. Five thousand years ago, a strange evil killed a good part of a nomadic people living between Eastern Europe and Central Asia. Those who did not become sick later settled in the area around the Baltic Sea and were known as the Vikings. They and their offspring could have survived thanks to a genetic mutation present today in several inhabitants of the Baltic countries, certain regions of Europe, Ukraine and Sicily.

What is the explanation? HIV enters the human body through lymphocytes and white blood cells. A subset of these lymphocytes, called CD4, plays a fundamental role in maximizing the defense capabilities of the immune system. It has on its surface a receiver called CCR5. It is the one that binds to the virus and allows its entry into cells by initiating contagion, and it is also one that is not present in some of the European heirs, who because of this characteristic their immune system prevents the pbadage of HIV. [19659002] The importance of the CCR5 receiver has been demonstrated almost simultaneously by two research teams, one Belgian and the other American.

For Hütter, the geographical distribution of this defective gene is "interesting". In the Baltic Sea and parts of Russia, there are frequencies of up to 10% or 15% of people carrying the gene and between 1% and 2% of them carrying it by their father and their partner. mother. It is activated. The frequency decreases to the east and the south.


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