Conferencia online 22/01/2010 Dra Judy Mikovts sobre el XMRV

[MaryP]

Primera presentación online (en Inglés) de la Dra Judy Mikovts del Whittemore-Peterson Insitute sobre el XMRV.
Esta será la primera presentación dirigida a los pacientes desde la publicación de su artículo en Octubre del 2009. La Dra Mikovts responderá a las preguntas del público presente y responderá también a preguntas enviadas con antelación por investigadores y pacientes de todo el mundo.

CITA ONLINE: La transmisión será en http://www.prohealth.com" onclick="window.open(this.href);return false; el viernes 22 de Enero a las 23:00 horas (hora España peninsular)

Para las personas fuera de España: la cita es a las 2- 4 pm US Pacific - 22.00 GMT. Pueden usar World Clock Time Converter (http://www.timeanddate.com/worldclock/converter.html" onclick="window.open(this.href);return false;)
y hacer la conversión de esta hora en U.S.A. California a su respectiva zona horaria.

[Miguel]

Por favor,en cuanto tengais una traduccion ponerla en el foro.Gracias por vuestro esfuerzo.

Es una lastima esto de no hablar nada mas que castellano y malamente.

[Merce]

De momento sólo ha salido un video de la primera media hora.
Por cierto, MIkovits, en el minuto 5 ,nombra dos veces Barcelona y algo mas tarde España, pero yo sólo entiendo frases sueltas.
Primero hace una presentación Annette Whitemore, creo.
Ayer vi el final en directo, pero lo mismo, sólo cojo frases y palabrs sueltas.

http://www.ustream.tv/recorded/4153940" onclick="window.open(this.href);return false;

[MaryP]

Hola!
Yo estuve siguiendo el seminario este viernes y desafortunadamente hubo un problema con la transmisión online y sólo se pudo ver esa primera media hora y las preguntas del final.
Efectivamente en la primera parte estuvo la introducción a cargo de la directora del Instituto y luego la Dra. Mikovts empezó su seminario con una introducción que incluyó una explicación de trabajos previos que llevaron al estudio del XMRV en SFC.

En un foro ya han hecho una transcripción de los primeros 27 minutos(en Inglés). Es decir, de la parte que pudo verse online y que ahora está colgada en página:
http://forums.aboutmecfs.org/entry.php? ... Pro-Health" onclick="window.open(this.href);return false;

Y un resumen de las preguntas y respuestas (también en Inglés):
http://forums.aboutmecfs.org/showthread ... Jan/page23" onclick="window.open(this.href);return false;

Vale la pena esperar a que cuelguen el seminario completo, se cortó la transmisión justo cuando empezaba a explicar los métodos de su estudio y seguro habló de los últimos avances. Por la sesión de preguntas se puede ver que han habido novedades después de Octubre.

Un saludo a tod@s,
Mary

[Merce]

Las palabras de Annete Whittemore antes de dar la palabra a Judy MIkovits


Es un placer estar aquí y tener la oportunidad de hablar con ustedes sobre el
reciente descubrimiento de XMRV en pacientes con síndrome de fatiga crónica.
Gracias por invitarme con Judy Mikovits hoy. Hemos hecho un esfuerzo especial para
aprender más acerca de la noticia más emocionante en el mundo del síndrome de
fatiga crónica desde la década de 1980 cuando los grandes brotes de esta
enfermedad se registraron en varios lugares de los EE.UU. incluyendo tres
pequeñas ciudades en Nevada.
>
> Los informes se produjo inmediatamente después del descubrimiento del VIH y el
SIDA. Durante este tiempo el Dr. Mikovits estaba en el Instituto Nacional del
Cáncer de trabajo en los laboratorios que estaban estudiando activamente este
nuevo virus que comenzó su programa de doctorado en la Universidad George
Washington. De hecho, escribió y presentó su tesis doctoral en la latencia del
VIH, presentado el mismo día que Magic Johnson anunció que era VIH
positivo. La buena noticia es que sigue siendo saludable después de todos estos
años, habiendo tenido la oportunidad tal vez para evitar una carga viral elevada
nunca ocurriera.
>
> Salto hacia adelante a 1989 trae un evento fundamental para la vida de nuestra
familia. Nuestra hija se enfermó y de repente nos encontramos en un agujero
negro de la medicina en el que nadie parecía estar de acuerdo en nada tienen que
ver con una enfermedad que se ha denominado 'Crónica de EBV. El problema era que
no tenía EBV o incluso los anticuerpos que habría indicado que había estado
expuesta a ese virus. Al igual que usted, buscamos respuestas, sino que nos
encontramos confusos e incluso absurdas teorías acerca de su enfermedad. Y así
comenzó el viaje en busca de respuestas.
>
> Todos tenemos distintas etapas de ese viaje. Nuestra primera y, probablemente,
uno de nuestros hitos más emocionante fue la reunión el doctor Peterson, que en
ese momento era rpomising que haría todo lo posible para ayudar a Andrea y para
ayudar a esta familia. Nuestro segundo hito fue realmente reunión, el Dr.
Mikovits. Y eso fue un encuentro maravilloso y tal vez profética. Estábamos en
una conferencia internacional y que había venido como invitada del HHV-6 de la
Fundación que oyó una charla muy importante sobre un conjunto de pacientes que
estaban desarrollando una rara forma de cáncer. Dio un salto de fe con nosotros
para desarrollar un instituto de investigación médica cuando la invité a venir a
Reno y el resto es historia.
>
> Judy traído con ella una pasión científica para el descubrimiento de la
verdad, y una curiosidad, con bien enseñaron técnicas del laboratorio del Dr.
Francisco Rosetti, el co-descubridor del primer retrovirus HTLV-1. Judy tiene un
temperamento fogoso y un corazón de oro. Y cuando no está CFS asesoramiento y
los enfermos de cáncer, ella enseña a los estudiantes, diseña experimentos y
viaja a las principales conferencias y universidades para educar a otros acerca
de las complejidades de los métodos científicos utilizados para buscar y
reproducir XMRV infecciosas en la sangre de los pacientes con SFC.
>
> Antes de presentar a Judy, me gustaría pedirles tres cosas de usted.

>
> En primer lugar, por favor, manténganse involucrados y reclamen por sus derechos,
el tratamiento médico adecuado y una financiación de la investigación. Sus
congresistas y senadores necesitan de saber de usted.
>
> En segundo lugar, por favor, mantenganse informados y educado. Escuchar
críticamente a lo que se dice y quien está entregando el mensaje. ¿Están hablando
en su nombre?
>
> Y en tercer lugar, quiero que sepan que el WPI va a continuar su misión
prometida. No vamos a parar hasta encontrar las respuestas, pero no podemos
hacerlo solos y seguimos necesitanto por su apoyo y su ayuda.

Apreciamos mucho todas las donaciones que han llegado, todos los buenos deseos
increíble que han llegado en nuestro camino, y queremos dar las gracias a
ustedes hoy en todo el mundo para las cartas que han llegado a apoyar este
esfuerzo, que realmente me ayuda.
>
> Así que ahora es mi voluntad a presentar a la Dra. Judy Mikovits, director de
investigación de la IPM.
>

[carpunia]

Mil gracias Merce. Hasta aqui al menos nos da esperanza, sensación de rigor y es muy convincente.
Seria estupendo enterarnos del resto de la charla y más estupendo aún, que lo que pasó ahí ese día sea para que se enteren los que realmente se tienen que enterar y se abran todas las puertas de par en par en este asunto.
Ferzas y besos para todos.
rocío

[elipoarch]

Colgaran el video un día de estos en su web. Hay que esperar.

[Merce]

http://www.prohealth.com/library/showar ... ibid=15114" onclick="window.open(this.href);return false;

[Merce]

Transcripción de la parte siguiente del vídeo (minuto 17 a 40)

(Anteriormente se colgó el minuto 1 al 17.Varias personas se han puesto de acuerdo para irlo transcribiendo por partes, seguro que mañana ya está todo hecho..Una vez transcrito se trata de darle al traductor automático..)

Judy Mikovits
Section 2 (Video #1: 27+ mins to 40:08)

On some of these patients we looked three and four times for the DNA in the unstimulated cells. So this is just that pellet that I made when I sorted all the various samples. I just held one as white cells so that I could make DNA later or RNA later, depending on the technique I wanted to use downstream. So, it’s important that this was in 68 out of 101 samples. It was 68 out of 101 patients and it clearly says that in the paper. So, at any given time, depending on the viral life-cycle, we might not find this virus in the unstimulated group (inaudible). And I give you the example of that is: follow this patient 1118 throughout the talk and you’ll see that this patient, if you only use sequences, would have been called ‘negative’. So, we were concerned because PCR is a technique that is fraught with contamination. If you’re looking for a needle in a haystack, just a few sequences in a million bases, you might make an error in your enzyme and it might put the wrong base in there.

So that…Jaydip Das Gupta in Bob Silverman’s lab, cloned and sequenced three of these patients – and that’s shown here – and what it’s intended to show is: If you compare the isolates that they had from the 3 prostate cancer cases, where they had actually cloned these, you can see, if you compare it to the reference strain, known as VP62, that’s the reference strain of what this virus looks like, the CFS samples here were clearly different, but they were highly similar - 99.7% - there were maybe 8 bases different across the entire 8,000 base pairs. So, this virus isn’t like HIV theoretically. It’s not changing. We don’t find quasi-species in patients when there are lots of different viruses, because HIV mutates so much. Therapeutically, that’s something that we can take advantage of and suggest that it might be easier to develop therapies because the virus is going to be largely the same.

So, Rachel Vagny, my former student at the National Cancer Institute – I asked her if she could construct what is called a phylogenetic tree of this virus so we could understand where it came from (hopefully). And so that’s shown on the next slide. And what a phylogenetic tree is - is you take all of the sequences of all the Murine Leukemia viruses - they’re called Ecotropic viruses – all the families of virus that they’ve ever identified, Mason-Pfizer Monkey virus, all the sequences, and you put them into the computer, and then you put into the computer at the same time the sequences of our 6 isolates – the 3 prostate cancer and the 3 CFS isolates that we had at that time. And you do what’s called ‘blasting’. You ask the computer to find similarities. And when it doesn’t find similarities, you get what’s called a new branch on the tree. So, clearly, these diverge here, and we don’t know when that is in time, but these data suggest that the prostate cancer – that XMRV both in prostate cancer and in CFS – form a new distinct branch. That it’s a new human retrovirus. It doesn’t have any of the sequences of mouse in it. And when we blasted it, also we did the same thing against the human genome - because I told you, we have a lot of endogenous viruses that don’t actually come out of our bodies as infectious particles – we blasted it against the human genome and found that it did not match any sequence in the human genome. So, it’s clearly a foreign, exogenous virus that can now, theoretically, be infectious. And that’s what we’ll show in the next slide.

So, here are our sequences. And you can see, they’re clearly not contaminants. We didn’t have this – we weren’t working with this in the lab, actually, at the time. But we didn’t have this, and maybe spread it through the sample in any way. It was there – clearly different isolates. We now have more than 170 isolates, because we isolate from every single patient in all of our studies. And we’re actively looking for funds and going to sequence those viruses because it might give us clues as to some of the differences in what we see, maybe something, you know the various symptoms, because CFS is quite a heterogeneous disease.

So, at any rate, we next went to – I’ll summarize that – So in summary, what is XMRV then? These data suggest, at this point in time, we have sequences related to XMRV that were not found in any mouse strain. So, it’s a new human retrovirus. The origin of XMRV remains unknown. We don’t know how it got into the human species. We don’t know how long it’s been – 40 years is the guess of John Coffin, who is a mouse retrovirologist working on these families of viruses for more than 40 or so years. And that XMRV is not a mouse virus – clearly from these data. So it’s a new human retrovirus.

So we next asked: Could we find those proteins I mentioned? So we took advantage of.. Sandy Ruscetti, Frank Ruscetti’s wife had been in retrovirology as long as he has, but because they didn’t want to work on the same thing, men usually get the credit for what women do, so Sandy worked on mouse viruses and Frank worked on human viruses and I don’t think they actually ever published together. But we were thinking about it and saying: None of the reagents that were out in the world, so far nobody had found viral proteins from XMRV, even though it had been discovered 2 or so years earlier. In January we started looking. So Sandy had saved a box of antibodies – this is really a tribute to the value of your tax dollars going to basic research – because they created this mouse retrovirology program and put a lot of money into trying to understand – if you can understand how viruses cause cancer in mice, you might understand how it causes cancer in humans. And this was in the late ‘70s and early ‘80s. And somewhere in the early 2000s, they were going to throw out all of these reagents that they developed and Sandy said, “No, I’ll keep them in my freezer.” Frank always says that the reason they’re still married is because Sandy never throws out anything. So, at any rate, she gave us these viruses, I mean these antibodies, and we screened our samples there for protein in our samples. So, we looked at the activated peripheral blood mononuclear cells. And what we do is, we stimulate these to divide, and add T-cell growth factor, or now known as IL2, which was actually the discovery that Frank made that preceded the identification of the first human retroviruses. Retroviruses grow and divide in cells, so you have to divide the cells in order to get the virus to replicate to levels that you can see with the technology of the time. And that’s important in this study too.

So, what we’ve got here is we looked a number of her antibodies – these are all family members of the virus – this particular antibody which you’ll hear a lot about is a spleen focus forming virus. It’s a mouse virus that causes various diseases including a neurological disease and erythroleukemia – red blood cell leukemia. So, its envelope is both a neurotoxin and an oncogene. It causes cancer and causes toxicity. So this virus itself – she had this antibody that was highly specific. It recognizes all known polytropic and xenotropic viruses. We hypothesized that it would recognize this virus and clearly high levels in some patient’s cells, but not in others. Interestingly enough, if you look, and use a panel of antibodies, this is a gag antibody to a gag protein I showed you there that structural gene and this virus, this antibody is a polyphone virus that recognizes the entire MULV. And you can see when you use a panel of antibodies to the viruses, essentially everyone, 68% now of 50 people we tried just one time, you could see their proliferating blood cells. You can see evidence of viral proteins.

So we next asked if we could see this in normal cells, because of course you want to make sure that it’s not in normal people. And you can see clearly here in the 24 normal donors (now up to 60 or 70 that Frank’s done) at the NIH clinical center where they have a good donor program – they’re all negative. So, these proteins, these viral proteins are expressed specifically in the CFS patients and not in normal donors.

So we next asked if we could transmit that. Is there any evidence that it’s an infectious virus? So the first thing we did was we took plasma – so that’s the plasma, the liquid off the white blood cells there – and we took their plasma and [this becomes essentially the key to the whole study] we co-cultured it. We simply put it in a flask with the cells known as LNCAP and that comes from lymph node-cancer-prostate. So this came from a lymph node of a 62 year old man who had metastatic advanced prostate cancer. And these cells grew by themselves in the laboratory so that you could use them as a tool for studying prostate cancer. And, in one of my lives, I developed prostate cancer drugs, because, when my stepfather got ill, I became interested in prostate cancer and had been working on this. So, I knew LNCAP was also deficient in RNase L, and the type one interferon pathway. It had no interferon response. So, we always look for biological multiplication of the virus instead of the multiplication you would use with PCR. So, actually replicate the virus or multiply the virus in cells. You have to find a cell that will grow a lot of virus so that you can study it. So we took that plasma from all of these patients you see high levels – now 84% of the plasmas contain infectious virus that we could not see. I sent all of these plasmas to Bob Silverman and he said, “Sorry Judy, I don’t see the RNA of the virus” there when he looked for the two copies of RNA in the particles which suggested there were very few copies of actual particles of virus in these cells. But again, we could transmit it.

And the next question we asked is: Is this a whole virus? Is this an infectious virus? Kun…Shima, my friend at the NCI who is an expert in Electron Microscopy, did this electron micrograph for me, and what you can see here is the budding of a virus from the cell. It shows you again that it’s not a contamination, it’s actually a transmission, because you’ve got a budding particle. And that particle is called a C-type retrovirus, because in the old days, when we used the word, they called them ‘C’ but they changed the name to gamma, but we’re old-fashioned, so we keep the ‘C’ type. [Ends at 40:08 in video #1]