[SUCCESSI] Il paziente tedesco II

Ricerca scientifica finalizzata all'eradicazione o al controllo dell'infezione.
Dora
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Iscritto il: martedì 7 luglio 2009, 10:48

Re: [SUCCESSI] Il paziente tedesco II

Messaggio da Dora » mercoledì 13 giugno 2012, 7:52

Leon ha scritto:Sono reduce da un piccolo esperimento: ieri sera ho preso un campione di acqua del rubinetto, l'ho messo nella mia macchinetta domestica per la PCR, l'ho fatta andare tutta notte a manetta e stamattina ho trovato il seguente referto:

Immagine

Qualcuno è in grado di interpretarmelo? Grazie!
:lol: :lol: :lol:
Grazie a te per questo esperimento così illuminante!
Adesso capisco meglio la storia del misterioso incontro con il procione verde fosforescente raccontata da Kary Mullis in Ballando nudo nel campo della mente.
Mullis non era assolutamente strafatto di acido come raccontano i suoi detrattori (e lui stesso in altri punti del libro), ma stava alacremente lavorando in laboratorio e facendo abbastanza cicli di PCR per testare gli estremi limiti della sua invenzione!!

Immagine



nordsud
Messaggi: 497
Iscritto il: giovedì 24 maggio 2007, 17:07

Re: [SUCCESSI] Il paziente tedesco II

Messaggio da nordsud » mercoledì 13 giugno 2012, 10:58

Leon ha scritto:Sono reduce da un piccolo esperimento: ieri sera ho preso un campione di acqua del rubinetto, l'ho messo nella mia macchinetta domestica per la PCR, l'ho fatta andare tutta notte a manetta e stamattina ho trovato il seguente referto:

Immagine

Qualcuno è in grado di interpretarmelo? Grazie!

Ma che bella contaminazione.
Sulla terra non esiste nessun laboratorio per la PCR esente da contaminazione. Più cicli si fanno più aumenta la contaminazione CHE C'E' SEMPRE IN UN QUALSIASI LABORATORIO FREQUENTATO DA ESSERI UMANI.
Tieni qualche cianfrusaglia fatta d'avorio in casa ?



Dora
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Iscritto il: martedì 7 luglio 2009, 10:48

Re: [SUCCESSI] Il paziente tedesco II

Messaggio da Dora » mercoledì 13 giugno 2012, 12:11

Non so se Lafeuillade, nella sua folle crociata autopromozionale, si sia reso davvero conto che stava parlando di una persona in carne ed ossa, con un volto ed un nome, a cui pure aveva tenuto la sua tronfia mano sulla spalla solo pochi giorni prima davanti alle telecamere.
Sta di fatto che ora arriva la reazione di Timothy Ray Brown (non un anonimo "paziente tedesco", sciocco e vanesio dr. Çaçaçaça). E, francamente, è molto difficile dargli torto.
Le dichiarazioni di Timothy sono state raccolte da Richard Knox, per SHOTS il blog dedicato alla salute su npr.com. Tralascio il resto del post, che ripercorre brevemente la storia di Timothy, la presentazione dei dati parziali della ricerca su di lui fatta a Sitges e le ragioni della "disputa", e riporto solo la parte finale:



Traces Of Virus In Man Cured Of HIV Trigger Scientific Debate

(...) AIDS researchers — and Brown himself, in an interview with Shots — stress that even if the new findings constitute real evidence of HIV in his system, they don't mean he's not cured. Although, it's clear the findings do raise questions about what sort of cure he has.

Scientists hoped Brown had a so-called sterilizing cure — that is, the HIV has been completely eradicated from every cell in his body.

But long and bitter experience with HIV has shown that the virus can hide out in the genes of very long-lived resting immune cells. As these latently infected cells get activated over the years, HIV might reappear in the form of the whole virus or perhaps pieces of its genes.

But if that is happening in Brown, there is no evidence that the virus is actively replicating. To do that, it would need to infect other cells and hijack their genetic machinery to crank out more virus. Since Brown's replacement immune system (from the bone marrow donor) doesn't have the entry portal HIV needs, these new viruses (if they exist in his case) can't spark a new viral conflagration.

Therefore, he may be functionally cured, even if he's not totally free of HIV.


That's what Brown himself thinks may be going on, from his discussions with researchers who have been poking and prodding him for the past five years.

"With a sterilizing cure, they have to be sure that a patient is completely clear of HIV — that they've looked everywhere and can't find any," Brown says. "In my case, I still have the dead virus and it's still showing up in some ways and so I've got a functional cure." [NdD: si attende a breve l'intervista promessa dal dr. Çaçaçaça, in cui smaschererà le balle raccontate a Timothy dai suoi medici. OMG!! :o ]

To him, that's just as good.

But Brown is distressed at the suggestion by some bloggers — in particular a French AIDS researcher named Alain Lafeuillade of the General Hospital in Toulon — that he's not truly cured.

"It's not the case, but people are spreading it," Brown says. "That concerns me because I've been told by many people that I give them hope — people who have HIV. And that's what I want to do. I want to be able to continue spreading my message and be able to do that without having conflicts of people who are misinterpreting the truth."

Brown is particularly upset at suggestions that he has become reinfected with HIV through unsafe sex. "That is not the case," he says. "It's very difficult for me to listen to those things and read those things."


The latest findings are sure to be debated among AIDS researchers and advocates. Their main significance is to show how tricky it will be to determine exactly what constitutes a cure, as researchers devise various tricks to cure AIDS with less drastic means than bone marrow transplants. The question is, when can they be reasonably sure a cure has occurred?

For his part, Brown says he'll continue to be a guinea pig for as long as it takes if he can help resolve that big question.

"Hopefully one day I won't have to do it any more," he says, because he'll just be one of many cured patients. "That would be nice."
[NdD: che Dio ti benedica, Tim, e ti conceda una vita bella e felice. Se c'è una persona al mondo che se ne è conquistata il diritto, quella sei tu. Immagine]



Leon
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Iscritto il: mercoledì 21 febbraio 2007, 7:33

Re: [SUCCESSI] Il paziente tedesco II

Messaggio da Leon » mercoledì 13 giugno 2012, 12:50

Dora ha scritto:For his part, Brown says he'll continue to be a guinea pig for as long as it takes if he can help resolve that big question.
SMETTILA, TIM! :evil: Chiudila con medici e ospedali, tanto non hai più né la leucemia, né l'HIV, fai un tour de force di qualche mese tra talk show, interviste esclusive e un bell'instant book "Io, l'unico al mondo guarito dall'AIDS, vi svelo il mio segreto" fatto scrivere in due giorni (e tradotto in tutte le lingue in uno) e poi vai a spaparanzarti definitivamente da qualche parte (bella), facendo perdere ogni traccia di te.



skydrake
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Re: [SUCCESSI] Il paziente tedesco II

Messaggio da skydrake » mercoledì 13 giugno 2012, 13:52

Leon ha scritto:
Dora ha scritto:For his part, Brown says he'll continue to be a guinea pig for as long as it takes if he can help resolve that big question.
SMETTILA, TIM! :evil: Chiudila con medici e ospedali, tanto non hai più né la leucemia, né l'HIV, fai un tour de force di qualche mese tra talk show, interviste esclusive e un bell'instant book "Io, l'unico al mondo guarito dall'AIDS, vi svelo il mio segreto" fatto scrivere in due giorni (e tradotto in tutte le lingue in uno) e poi vai a spaparanzarti definitivamente da qualche parte (bella), facendo perdere ogni traccia di te.

Immagine



Dora
Messaggi: 7502
Iscritto il: martedì 7 luglio 2009, 10:48

Re: [SUCCESSI] Il paziente tedesco II

Messaggio da Dora » giovedì 14 giugno 2012, 11:49

Dora ha scritto:Non so se Lafeuillade, nella sua folle crociata autopromozionale, si sia reso davvero conto che stava parlando di una persona in carne ed ossa, con un volto ed un nome, a cui pure aveva tenuto la sua tronfia mano sulla spalla solo pochi giorni prima davanti alle telecamere.
Sta di fatto che ora arriva la reazione di Timothy Ray Brown (non un anonimo "paziente tedesco", sciocco e vanesio dr. Çaçaçaça). E, francamente, è molto difficile dargli torto. (...)
Una aggiunta di oggi dai commenti al blog di Richard Jefferys (non so quanto mi ci vorrà per digerire lo scandaloso esibizionismo di Lafeuillade):

Immagine



Dora
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Iscritto il: martedì 7 luglio 2009, 10:48

Re: [SUCCESSI] Il paziente tedesco II

Messaggio da Dora » giovedì 14 giugno 2012, 11:52

Dora ha scritto:
Leon ha scritto:P.S. Con riferimento all'altro post, la storia che le staminali del cordone presentassero minori problemi di compatibilità non l'avevo mai sentita prima; l'ho letta nell'articolo e l'ho presa per buona anche se, nel caso sia proprio così, non riesco nemmeno lontanamente a intuirne i motivi.
Ieri ipotizzavo dipendesse dal fatto che il sistema immunitario del feto non è ancora completamente formato.
Ora, senza andare a leggere articoloni, ho cercato una spiegazione e ho trovato che le staminali prese dal sangue del cordone ombelicale sono biologicamente più giovani e “flessibili” di quelle adulte, prese da altre fonti quali il midollo, e presentano meno rischi di complicanze durante il trapianto.

Qui scopriamo qualcosa di più su questa “flessibilità”:
  • How Do Cord Blood Stem Cells Differ From Other Stem Cells?
    Cord blood cells hold advantages over other types of stem cells. Umbilical cord blood stem cells are considered the 'freshest' and 'youngest' stem cells available. They also avoid the ethical debate surrounding embryonic stem cells because cord blood cells do not involve the destruction of an embryo. In addition, cord blood stem cells hold an advantage over adult stem cells because they do not have the DNA mutations that the 'older' adult stem cells may have developed over time.
    Another benefit of cord blood stem cells relates to a condition called graft versus host disease (GVHD). This is actually a fairly common complication that arises following a transplant that is allogeneic. Allogeneic refers to a transplant involving cells from cord blood or perhaps another family member or an unrelated donor. The consequences of GVHD can be mild or fatal. Research has shown some positive findings, however, in that following a cord blood transplant, fewer patients suffer from GVHD than those who receive other transplants such as bone marrow. Those who do suffer from GVHD after receiving a cord blood transplant tend to have milder symptoms.
(Da http://www.explorestemcells.co.uk/cordb ... cells.html)

Ho trovato anche una breve review (Umbilical cord blood for allogeneic transplantation in children and adults) in cui si conferma che con le staminali prese dal cordone si ha una ripresa più rapida dal trapianto, con minore incidenza e severità di episodi di GvHD.

Inoltre, queste cellule sono destinate a vivere più a lungo delle staminali adulte e hanno maggiori probabilità di proliferazione.
Qualche informazione in più sul trapianto di staminali prelevate dal sangue del cordone ombelicale:
  • Lawrence Petz, chief medical officer of the California blood bank StemCyte, has been collecting cord blood stem-cell samples that have the CCR5-delta 32 mutation. He said he has 102 samples and hopes to expand to 300 samples, so HIV-positive people in need of a stem cell transfusion can search for a match.

    Cord blood stem cells function like bone marrow stem cells but are easier to match. (...)

    StemCyte has recently sent stem cells to a patient in the Netherlands for a transplant. Although they have to wait a couple of months to test for HIV, Petz is optimistic that a second patient could be cured.
**********************************************

Aggiungo che fra poco più di un mese, all'IAC di Washington, verrà presentato un lavoro il cui titolo fa davvero ben sperare, perché potrebbe anche aggiungere in corsa i risultati preliminari del trapianto al "paziente olandese" di cui parla Petz:



stealthy
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Re: [SUCCESSI] Il paziente tedesco II

Messaggio da stealthy » venerdì 15 giugno 2012, 8:06

Ieri Timothy Brown ha partecipato a un incontro sulla prevenzione a Philadelphia e ha tenuto un discorso.

Nell'articolo sotto si dice anche che parlerà davanti a Obama e al Congresso perché diano più finanziamenti alla ricerca.


Immagine

Da newsworks.org






Dora
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Re: [SUCCESSI] Il paziente tedesco II

Messaggio da Dora » martedì 19 giugno 2012, 21:20

Myles Helfand ha pubblicato oggi su TheBodyPRO una lunga intervista a Gero Hütter, che si trovava a New York per una conferenza, e si è fatto raccontare il caso del "Paziente Tedesco" dal suo punto di vista: come l'ha affrontato, come ha valutato rischi e benefici, le lezioni che se ne possono trarre, che cosa deve accadere perché il successo si ripeta.


HIV Frontlines: The Doctor Who Cured HIV


Immagine

The Makings of a Miracle

  • Explain to me how a clinician who is trained as a hematologist and a cancer researcher ends up being the guy who changes the way we think about the approach to an eventual cure for HIV.


[Laughs] This is what I always want for my patients: I want the best treatment. This was a challenge, from when I saw Timothy and I realized that we have to do this transplantation. For me, it was the first patient with HIV which received allogeneic transplantation.
We know from patients with leukemia that eradication is achievable. And we cannot accept, in patients with leukemia, that any of these leukemia cells will survive, because they are the basis of any relapse of leukemia. So you have to cure these patients and get rid of the leukemia. And if this works with leukemia, why shouldn't it work with HIV?

  • You make it sound like it's such a natural, logical conclusion. But we've known about this mutation -- that people whose CD4 cells don't have the CCR5 receptor are largely immune to most forms of HIV -- we've known this since the mid-to-late '90s. Yet nobody had thought to try this before.


That's not quite correct. There are several others who had this idea before me. And they had made approaches to realize that. For example: the StemCyte [Cord Blood Bank] built up cord blood units, with tested cord blood units for the CCR5 mutation in 2001.
The gene therapy approaches targeting CCR5, they are older than the Timothy Brown case. But this case has supported their work. The techniques were available, and the idea was available, but it needed something that enhances the whole development.
After the Timothy Brown case was published, the funding and the support for such new approaches were opened, and now the development has come much more quickly and rapidly.

  • When you first thought to do this, this was a shot in the dark, right? Timothy's prognosis was pretty grim. No one had actually attempted this type of treatment before. Did you think, "Might as well give it a shot"?


Yeah. I would have felt better if I had tested it before. [Laughs] I knew it was probably possible. It's not easy to test the same condition in animals, but you could see some effects in animals.
In this case, it was clearly a shot in the dark. I studied the literature. I looked in PubMed, up and down, to see if there was anything published on this point: What happens if a patient who is HIV infected changes the CCR5 phenotype? And I found absolutely nothing. It's never been tested before, not even in vitro.
This was very surprising. It could be that no one really thought about this possibility. And the other explanation could be that they have tested it, it's gone wrong and no one got published. I was a little bit nervous about this point.
We were a little bit scared that we didn't really know what could happen: You have high selective pressure against the virus, when we changed this immune system to CCR5 depleted cells, and no one really could say how the virus would behave.
[But then we realized that] the worst thing would be that he changes his tropism to the CXCR4 receptor, and then as long as he takes his antiretroviral medication, there's no harm for the patient. So we got optimistic that we could dare this experiment and that the risks are not too, too big.

  • I think it's easy for a lot of us to grasp on to this and say, "Here is the cure. Here is the future. Here is where it's going to happen." I'm guessing you've heard this kind of question a lot: "Is this the path forward?"


Yeah. If you look at the HIV research, we have no better answers for cure questions than what we have now with the CCR5 receptor, gene therapy. We have approaches in targeting, unmasking and killing, specifically, reservoir cells. But they are all connected with the cure question.
And the cure question, 10 or 5 years ago, was no real question. If someone said to you, "I want to cure HIV," all you'd have to say is, "You're mad. This is not possible. This is a retrovirus which degrades, and you can't get rid of the genomic material." This was the dogma of this case.
The way of thinking about cure has changed a little bit. This makes the process open for alternatives to the current antiretroviral therapy -- it does not have to be only the stem cell approach. There are other approaches derived from this case, which are also promising.

  • We've known for a while that the CCR5 receptor is the primary way through which HIV enters a CD4 cell. But there's still so much that we don't really know about the CCR5 receptor. How much have we learned over the past few years?


Very little. We know that the CCR5 deletion is much older than HIV, and the mutation appeared thousands of years ago. The distribution, what we see now -- in Europeans, this deletion is high; in Africans and Asians it is absent -- this is a distribution which happened in the last 10,000 years. There must be some kind of advantage for these carriers, and we don't know all the reasons why.
We don't know exactly the function of CCR5. We know that it probably plays a role in another infection, the West Nile virus infection. But all of the details are very unclear. There are some studies focusing on carriers of the CCR5 deletion, and whether they have high risk of any other disease. But these associations are very weak; there's no clear association of any disease with the deletion.

  • Why hasn't there been a Patient No. 2 yet?


We have had requests from other institutions -- taken together, I think we have now 15 other patients with HIV in need of urgent transplantation, because of leukemia, lymphoma, and so on. And some of them had just one [potential donor match]. Who gets that donor that was tested and was CCR5 negative?
Some had many potential donors -- 60, 120, such as Timothy had -- but sometimes mathematics fail. And the probabilities [of success] are 1 percent.
So this is a problem. I think it's a question of time. If you wait long enough, you will find a patient who will have the same conditions like Timothy.
The other point is that we don't have access to every patient who has the possibility to do this. There are many more patients with HIV who get transplants by allogeneic transplantation than we get information about. Because some institutions didn't really know about [the Timothy Brown] case. Some knew about this case and said, "Oh, this is so uncommon, this mutation; it doesn't make sense to test for it." They didn't start with it. If you don't start with the investigation, you will never find a second patient.
This is the biggest problem, I think: We have information about less than 5 percent of all these patients who get transplantation. If we have access to all of these and test them, the probability is much more higher to find a second patient.

  • Is this a uniquely European thing that you did? Could what you did with Timothy Brown not have been done anywhere else?


No: They tried it, too, in the U.S. But the circumstances are not like in Europe, or especially not Germany. We have in Germany a unique situation: We have 80 million Germans, and 3.5 million of them are registered in donor registries. It's very high. It's the highest proportion in the whole world.

  • Do you know how that compares to the U.S.?


You have 7 to 8 million in the U.S. But the difference, the second difference, is: These 8 million in the U.S. are derived from hundreds of stem cell registries. Every county, every state, every hospital, every institution has its own registry. And in Germany we have a central registry for all of these. So it's much easier to assess these registered donors.
That's also the reason why it works so well. You can do this in any country, but it works so well [in Germany] because we have this central registry, with a large number of registered donors. This was part of the success.



The Evolution of a Cancer Doctor

  • How many HIV-positive cancer patients had you treated before you met Timothy?


None.

  • Was he the first HIV-positive patient that you had interacted with?


No. I've seen many HIV patients, through my students and sometimes my medical training. But most HIV/cancer patients, they are old patients or they are in other departments with specialized HIV treatment. It's uncommon that an HIV patient would come to our department. It's only the case if they have diseases like leukemia or aggressive lymphoma, which cannot be treated by other institutions.

  • The bulk of your practice and the bulk of your research: Where had that been focused on, up until 2006?


My research focus was on leukemias, on resistance against chemotherapy and stem cell treatment.

  • Had that always been your passion? Or is that something that developed out of your education?


It has a little bit development, but I started with my scientific area with my doctoral thesis. It was based on resistant phenomena against chemotherapy.

  • How much of your clinical and research focus has continued to be on chemotherapy resistance since news of Timothy Brown broke?


Now I'm not working clinically anymore. I changed my position to an institution which specially is for collecting and producing stem cell products or other blood-derived products. This is not clinical work. A great part of my work is now research.

  • Is it research on how stem cells can be used to treat all diseases, or does it focus specifically on HIV?


It's for other diseases. But part of this research project is how to use it in the case of HIV, yes.

  • What kind of research have you been able to do?


We have focused on the molecular things which are associated with the CCR5 deletion. Because not everything is quite clear about this deletion -- why some effects are also measurable in the transplantation setting. We know that people who have this deletion, the CCR5 deletion, they have better survival if they receive kidney grafts, after kidney transplantation. Normally, transplantation of the kidney has a survival rate of 5 to 10 years. People who have this mutation, their kidney will not be rejected.
So CCR5 deletion is part of this effect in nature. We have other immune system phenomena which have not really described what's behind this phenomenon.

  • Where is your research focused right now?


Our stem cell unit is focused on treating this population of hematopoietic stem cells for hematological patients. But we have also done research on mesenchymal stem cells, which can be used for regenerative medicine. This whole stem cell area is covered from our institution.

  • Is regenerative medicine the idea that, if you lose a finger, it can grow back the finger? Or is that a little far-fetched?


I think this is not going to be in the next few decades. It probably is not possible. But you can replace part of tissues if you have injuries, or loss of some special tissues. Or you can rebuild a heart muscle, with mesenchymal stem cells. These cover small areas of possibility; it's very hard to rebuild whole organs, or limbs. This is science fiction, I think.

  • But if you're an HIV/HCV-coinfected person, and you're cirrhotic, is there a potential that down the road this kind of research can lead to some liver regeneration?


Probably. I don't know -- I wouldn't exclude this possibility.



Looking Toward the Future

  • Before you came here this morning, you gave a talk at St. Luke's-Roosevelt Hospital Center. What was it about?


I covered the Berlin patient story: what things we already know from the results; what is unclear and what is not detected; what are the consequences of the case; and how we can go on with this approach.

  • How many of these talks have you given over the past few years?


[Laughs] Oh, many. I like the idea of promoting the CCR5 story. Many people have heard of it, or read. But I think there are some details which are still [not known] for many people who didn't read it very carefully and have [ideas] of this case which are not quite true. So it's probably good to remember, then, what are the facts, and what can we learn from this case.

  • In addition to not knowing the details of the Berlin patient case, you mentioned earlier that some medical instiutions don't think to test allogenic transplant donors to see if they have the CCR5 deletion. Is that one of the reasons that you've been speaking -- to try to increase that level of education and communication?


Yeah. I want to promote the fact that we can do this testing for free [at our institution]. Someone will say, "Oh, no. Don't do this testing; it will cost us too much."
I say, "No. It doesn't cost anything. I will cover all the costs." But they are always unsatisfied. Some say, "Yeah, we have such a patient. But we want to do this testing alone. We don't need your help."
They have made, here in the U.S., a trial for patients where they specifically look for CCR5-deleted cells, and for a few patients with leukemia and so on. It's an NIH [U.S. National Institutes of Health] trial. And all of [the people involved in] this study hadn't made contact with me. I found out about it from their presentation at CROI that they started it.

  • So you just hope that you make the connections and that ultimately it will start to come together.


I'm hoping for everything. I support every work which is in this direction. So, go on, if you have patients.



stealthy
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Re: [SUCCESSI] Il paziente tedesco II

Messaggio da stealthy » martedì 19 giugno 2012, 22:25

Dora ha scritto:[...]

  • Before you came here this morning, you gave a talk at St. Luke's-Roosevelt Hospital Center. What was it about?


I covered the Berlin patient story: what things we already know from the results; what is unclear and what is not detected; what are the consequences of the case; and how we can go on with this approach.

  • How many of these talks have you given over the past few years?


[Laughs] Oh, many. I like the idea of promoting the CCR5 story. Many people have heard of it, or read. But I think there are some details which are still [not known] for many people who didn't read it very carefully and have [ideas] of this case which are not quite true. So it's probably good to remember, then, what are the facts, and what can we learn from this case.

  • In addition to not knowing the details of the Berlin patient case, you mentioned earlier that some medical instiutions don't think to test allogenic transplant donors to see if they have the CCR5 deletion. Is that one of the reasons that you've been speaking -- to try to increase that level of education and communication?


Yeah. I want to promote the fact that we can do this testing for free [at our institution]. Someone will say, "Oh, no. Don't do this testing; it will cost us too much."
I say, "No. It doesn't cost anything. I will cover all the costs." But they are always unsatisfied. Some say, "Yeah, we have such a patient. But we want to do this testing alone. We don't need your help."
They have made, here in the U.S., a trial for patients where they specifically look for CCR5-deleted cells, and for a few patients with leukemia and so on. It's an NIH [U.S. National Institutes of Health] trial. And all of [the people involved in] this study hadn't made contact with me. I found out about it from their presentation at CROI that they started it.

  • So you just hope that you make the connections and that ultimately it will start to come together.


I'm hoping for everything. I support every work which is in this direction. So, go on, if you have patients.
Bella intervista e risposte molto schiette e semplici.

Ho quotato quest'ultima parte dell'intervista perché ritengo che il suo messaggio sia molto chiaro. Promuove il caso di Timothy e allo stesso tempo spingere i vari centri a creare dei database specifici affinché si possano trovare dei donatori con la delezione CCR-5.
Bravo dott. Hütter!



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