Thursday, May 31, 2012

細胞治療 治癒 愛滋病 !! (targeting mutation CCR5-delta 32 approach)


The first cure of AIDS by cell therapy   Author: Dr. Isabella Catala   May 30, 2012   Marseille, France - For marital status, it is Timothy Ray Brown, an American from Seattle. For the community of virologists, he is known as the "Berlin Patient", the first person considered cured of AIDS worldwide. Hope for researchers. But a case which should remain fairly unique as the treatment he received is unique and impossible to imagine a large scale.   On the occasion of the congress è s ISHEID 2012 (International Symposium on HIV & Emerging Infectious Diseases), Timothy Ray Brown and his hematologist, the Dr. Gero H ü tter (Württemberg, Germany), have detailed experience of a human point of view and medical.

HIV positive since 1995, treated since 2002   "I would say one day that I am the first patients who have recovered from AIDS ... Do not be a unique case," said Timothy Ray Brown. "In 1995 when I was studying in Germany, I discovered my HIV status. I then received treatment from 2002 which, despite side effects, enabled me to live a life that I found acceptable.   But in 2006, I felt tired. Blood tests showed that I was suffering from anemia. Leukemia was diagnosed. Dr Gero Hütter, my hematologist in Heidelberg I was offered treatment with marrow cell therapy associated with that, he said, could heal me both AIDS and leukemia. I refused. I wanted to do with chemotherapy. 

Relapse and two transplants   But two years later, it was a relapse. There I am willing to lend the graft and the technique for transplanting stem cells selected for mutation in CCR5, which I had already been proposed and which the doctors did not guarantee me provided a definitive result. I had two bone marrow transplants with the same donor, during the second, I presented neurological complications that I have left a legacy to this day.   Today, doctors performed on all samples imaginable me, they looked for viruses in all parts of my body, have punctured all that was possible to drain. And I was declared cured. I hope to be the first in a long list and that the suffering I have endured will give hope to others. Now I want to share my experience to as many people to sensitize decision-making powers to the importance of following the tracks of different therapeutic drugs alone. " 

Targeting donors with a homozygous mutation CCR5-delta 32   This testimony, while emotion and sensitivity, has been supplemented by a more scientific approach of the treatments proposed by the team of hematologists who have supported. "The idea of ​​treating HIV with cell therapy is old: it could help prevent complications of infection by substituting the CD4 immune cells to the virus. But we had to dispose of resistant cells, which was not the case for nearly two decades, "says Dr. Hütter.   It was not until 1996 that the first resistance gene was discovered. The CCR5 receptor which binds the virus from patients with homologous mutation of the CCR5 receptor-delta 32 CD4 becomes inactive. HIV can not bind and the infection is impossible. This mutation is heterozygous worn so by 10 to 20% of Caucasians and homozygous by only 1% of that population, with a greater presence in the Baltic States, Britain and the countries of northern Europe. It is completely absent in Africa, Asia and India. 

Proof of concept. Work on the entry of the virus   "When Timothy Ray Brown came to consult me, I offered a bone marrow transplant. My idea was to find a donor homozygous for the CCR5-delta 32 mutation, to make it insensitive to HIV also he was carrying. The patient himself was heterozygous for this gene. Among the 232 HLA identical donors, only one was eligible because of its homozygosity. Two months after the two bone marrow transplants, we found a complete change in its genotype CCR5. The virus persisted several weeks in the peripheral blood and then became undetectable. The antibody level was also lowered. The rate of CD4 is plus.   We then searched for the virus in lymph node reservoirs, digestive and CSF. We have never detected virus activity. It is unrealistic to expect that this treatment is possible for a majority of patients: it is the marrow whose complications can be fatal. On the other hand, the number of potential donors is very low. But it's still the first time we prove that it is possible to cure AIDS. Today, after this proof of concept, two other patients received a transplant of the same type and track their evolution will give us some basic information. This transplant could also inspire us to work on ways to block viral entry into the cell. Tracks are already developed in this direction, "concludes Dr. Hütter.

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