Re: Farmas USA
OCAT
Ayer hubo presentación de Lanza. Lo asaltaron luego los inversores y le sacaron que la publicación de los nuevos datos no tardará: "publication on the Korea data is not even weeks away"
Entre las citas destacadas está esta, porque OCAT es la úica empresa cuyos ensayos son con células diferenciadas; todo el resto usa indiferenciadas, por lo que no descartan la aparición de teratomas.
Of course if you transplant undifferentiated embryonic stem cells, you would get the teratomas, but by contrast, once they are differentiated and the telomerase is turned off, you can transplant the RPE, even if they are spiked with out to 1% undifferentiated cells, we do not see any teratomas whatsoever.
Esto es información que creo que no se conocía:
We have recently generated an IPS line from O negative for an O negative individual so that the blood that we generate is now universal blood, so that means that we can transfuse that blood into virtually everyone in this room, so we wouldn't need to type the blood.
La conferencia entera, por si a alguien le interesa:
Dr. Robert Lanza, UConn Stem Cell, April 27, 2015
Transcript By, Patti
1. It's a great pleasure to introduce Dr. Robert Lanza who is the Chief Scientific Officer at Ocata Therapeutics and Professor at the Institute for Regenerative Medicine at Wake Forest University School of Medicine. He received his undergraduate and his medical degrees at the University of Pennsylvania and he has written 100's of publications and over 30 books. We are very fortunate to have him here. He has made very important breakthroughs in the field of regenerative medicine. Notably, he and his colleagues published the first report of pluripotent stem cell use in humans. They have pioneered differentiated pluripotent stem cells into a very special cell type in the retina, the retinal pigment epithelial cell, a critical cell type that is often affected in diseases causing blindness. They have received FDA approval for clinical trials transplanting these cells into patients to treat eye disease. He has received numerous awards including Time Magazine's 100 Most Influential People in the World. So please join me in welcoming Dr. Lanza, whose talk today is entitled "Moving the first pluripotent stem cell therapies to the clinic."
2. Thank you very much for that kind introduction, and I'd like to thank the organizers for having me here today. As I mentioned, I will be talking about moving the first pluripotent stem cell therapies into the clinic.
3. First I need a cautionary statement and mention that it may contain some forward looking statements.
4. As you know, there are two major hurdles in regenerative medicine, namely the problem of tissue shorters, as well as the problem of immune rejection, and with the advent of pluripotent stem cells, we now have before us the opportunity to bypass both of these hurdles. So in addition to the shortage of organs, such as kidneys and livers, there are literally 100's of diseases caused by tissue loss of dysfunction. Many of the very first pluripotent stem cell therapies to move into the clinic are likely to involve what we call immune privileged sites, such as the eye and the central nervous system so that you can use off-the-shelf cells, and of course in the eye, visual disorders such as AMD affect about 15 million people in the United States alone (For ref. see previous slide #4 - Cowen and Company 35th Annual Health Care Conference, Boston, MA, March 3, 2015). In the central nervous system, of course, there are many disorders such as Parkinson's, strokes, spinal cord injuries, multiple sclerosis, and these cost the US economy literally $100's of billions of dollars every year. At Ocata Therapeutics were are focusing on the eye. We are currently in clinical trials using our retinal pigment epithelium, or RPE cells to treat macular degeneration, but we also have a number of other therapies we are hoping to move into the clinic very soon, including retinal ganglion progenitors to treat glaucoma and other optic neuropathies, corneal epithelium for corneal disease, mesenchymal stem cells, as well as retinal photoreceptor progenitors.
5. This is just a cartoon of the eye just to let you have an idea of what's going on. So the light enters the eye and it hits these photoreceptors, which are the cones and the rods that we see with, and underneath that are these cells, the RPE cells, and they are the lifeline of the photoreceptors. They have myriad different functions. They provide critical nutrients, growth factors, ions and water. They recycle photo pigments and Vitamin A. They phagocytose the photoreceptor fragments and these photoreceptors can shed up to 9% of their mass every day; so there are literally dozens of functions that are critical to the maintenance of the photoreceptors.
6. We have now successfully completed two Phase I/II clinical studies in the United States using these RPE, which were derived from human embryonic stem cells, and we have two studies in the United States, one using the RPE to treat dry AMD, and the other is to treat Stargardt's disease. Stargardt's is one of the leading forms of juvenile blindness, and dry AMD and its wet form, are the leading cause of blindness in the developed world. We have also carried out the only human clinical trial involving pluripotent stem cells in Europe. In that case we used RPE cells derived from embryonic stem cells to treat Stargardt's disease. AMD and SMD again are currently untreatable. Just for AMD alone, it is projected to affect 288 million people worldwide by 2040, and the total economic burden for visual loss and blindness is expected to reach $717 billion dollars by 2050.
7. Before we got FDA approval to begin the clinical trials, we obviously had to carry on IND-enabling studies, so we had to show in animals that these cells were safe and effective. So we studied the gold standard, the RCS rat and we were able to show that the transplantation of these RPE that we derived from the embryonic stem cells were able to restore visual acuity in these animals in a dose-responsive fashion, similarly show that the cells after they were transplanted subretinally could also prevent photoreceptor loss in the ELOV4 mouse, which is a Stargardt's model. Importantly, when you look at histologically what happened with the cells, you actually see that the human cells that were transplanted integrated very nicely into the host monolayer, RPE monolayer, and if you stained for anti-human stain cells, you can see that those are human cells, and then if you stain with the strobe gun, which is an RPE specific marker, you can see that they will also co-localize to that patch, which again has integrated into the host. Similarly, if you look at the RCS rat after 90 days, what you see is that the animal is blind. It's completely missing the outer nucleated layer. When you transplant these RPE cells that were derived from stem cells, you can see that there is a very robust rescue of this outer nucleated layer again being contained with the photoreceptors we see with that have been rescued. So we were hoping to see that kind of visual improvement in humans. Obviously of course the regulatory agencies, both in the FDA and in Europe, wanted to see safety before we went into patients, so we showed that there were no safety signals, either tumors or atopic tissue in any of the animals that we studied. We studied literally over 200 of these animals. We also followed some of the animals for their lifetime to show there was no teratoma formation, because again, these are master cells of the body and they can turn into virtually every cell type. One of the characteristics is they can form these teratomas that form all three germ layers.
8. Of course if you transplant undifferentiated embryonic stem cells, you would get the teratomas, but by contrast, once they are differentiated and the telomerase is turned off, you can transplant the RPE, even if they are spiked with out to 1% undifferentiated cells, we do not see any teratomas whatsoever.
9. Indeed, the manufacturing process does not allow that to occur. We developed an assay where we can detect even one undifferentiated cell in over a million of our RPE, and that's more than a single cell on even our highest possible clinical dose. So even if you spike in 10% undifferentiated cells made in the manufacturing process, you still don't end up with any undifferentiated cells. So that gave the FDA a lot more comfort to allow us to proceed with our clinical trials. We also got similar approval from the UK regulatory agencies.
10. So in the United States, we had four clinical trials, Mass Eye and Ear in Massachusetts, Wills Eye Institute in Philadelphia, Bascom Palmer in Florida, and Jules Stein in California, and we had two sites in the UK, Moorsfield Eye Hospital and Newcastle (Ireland). To date, we have treated 38 patients. We are just coming up to four years on those first patients.
11. So this just shows you the clinical trial design. Basically the dosage increases. We started with 50K cells and after we showed in three patients that that was safe, the Data Safety Monitoring Board approved us to move on. We culled the doses to 100K cells, then to 150K, and eventually to 200K. These patients were monitored using various methodologies include OCT, which is a very high resolution measuring device. You can actually look into the eye in real time and actually see what is going on in real time at the cell level, so if anything adverse was happening, we would know almost immediately.
12. So we published the follow up of our clinical trials just a few months ago in the Lancet. We found there were no safety issues related to the stem cell treatment in any of the patients. There were clear signs of long-term engraftment and survival. This is one patient you can see, this is the transplant site. Prior to transplantation there was no pigmentation, then you can see the appearance of these pigmented patches, the RPE, which continue to expand with time. Indeed, if you look at the patients on OCT, you can see this nice monolayer here, where the arrows are pointing, those are RPE cells that were not there prior to implantation, there actually were just maybe one or two cells at most.
13. During that follow up period, we actually found in both the SMD and the AMD patients that they had significant overall visual improvement in the treated eyes. Except for one patient, virtually all of the patients either improved or stabilized during that time period. By contrast, the untreated eyes did not show similar improvement in their visual acuity. And this just shows you an overview of the results, so this is the median visual acuity over baseline. So what you are seeing here with the dotted line is the untreated fellow eye. We treated just one eye, so the untreated eye you can see at 6 months and one year, there was no improvement in vision during that time period. By contrast, the eye that we treated with the RPE cells, here you can see that's the solid blue line. There were 15 letters of improvement in these patients. That represents about three lines of visual improvement in these patients. That's a double in visual angle and is generally considered clinically significant. And many of these patients, for instance, they could only detect hand motion. Within a few days they could actually start to see and count fingers. Eventually they could start reading letters on the visual acuity chart and indeed the first SMD patient that we had that could only detect hand motion, now is out over two years and can read 4 lines, 19 letters on the visual acuity chart, and she can use her computer. People can now go to the mall on their own, so this has made a significant difference in the quality of life for many of these patients.
14. In addition to the RPE program, we are also looking at other cells in the eyes. For instance, we have now been able to create large numbers of homogeneous retinal ganglion cells, very large numbers of these. We can also produce what we call these photoreceptor progenitors that can then go on to turn into mature photoreceptors. This just simply shows you that we get very pure populations of photoreceptors from both embryonic stem cells as well as from IPS cells, which are generated of course from either skin cells or any other somatic cell. So here in red, you are actually seeing some rods that were made from embryonic stem cells. In the green you can see cones that we generated from embryonic stem cells, and similarly rods and cones that we generated with the IPS cells. The IPS cells do these tricks just as readily as the ES cells. This just simply shows you if you look at an analysis of the transcripts, as you go from retinal neural cells to the photoreceptor progenitors, you see an up regulation of the (Radofsan, Offsen), and recovering, which is expressed in all photoreceptors. We transplanted these cells into a number of different animal models, so here you are seeing in green the human cells that we transplanted into the subretinal space of an RD1 mouse and they mature and actually integrated into the retina. After the integration, we actually carried out some studies to see whether it improved the function of these animals, so we looked at the animals that were completely blind. In this case, as I mentioned, it was the RD1 mouse, which actually lose their entire outer nucleated layer by 3 weeks. That means they have no photoreceptors left. We waited an additional several weeks and actually transplanted some of our photoreceptor progenitors at 10 to 12 weeks, and what we saw, and this is the optomotor test that measures visual acuity, what you do is you stick a mouse inside this drum that has these vertical bots and that drum can rotate either to the left or the right so you can actually measure either the left eye derived response or the right eye derived response, or you can treat one eye and not the other and see if it makes a difference. We actually show that we can get a very significant response in this optomotor test that was directly proportional to the number of cells that survived in the graft, and these again were completely blind animals. We also did what is known as a light avoidance test, and what you do is you stick a mouse in a chamber, a lit chamber, and there is a little aperture, and what you want to do is see if when you shine a light rather or not the mouse will try to avoid the light, and of course without any cells, the mouse does not obviously detect the light and does not go into the dark spot, but what we found is when we transplanted these photoreceptor progenitors, again we saw an increase in the light avoidance that was directly correlated with the number of surviving photoreceptor cells that we had transplanted.
15. We also looked at the RCS rat and what we actually found is when we injected the photoreceptors into the subretinal space, again the optomotor response here in green in the transplanted animals versus the untreated animals, so there was about a doubling in the visual acuity of these animals. We also did what is known as luminescent threshold response and you can see in the untreated animals in green, even at a threshold of 1.75 was no response to the light in the brain. By contrast, when we transplanted the photoreceptor progenitors, there was a very significant response.
16. This just show you can actually do electroretinogram in the eye, very similar to an EKG in the heart. What you can do is you can transplant for instance what you are seeing here in red, is one eye that was transplanted with the photoreceptor progenitors and in blue is the eye that did not get the transplant, and you are seeing a very nice B-wave response, which measures the host synaptic connections, and by contrast there was no response in the untreated eye and this is at two different light frequencies. Similarly, you can oscillate the light and see if the eye is able to respond, and here you are seeing the eye that was treated. You are getting a very nice response there in red. The untreated eye virtually no response to the oscillating eye. Similarly, you can carry out another, here's one where we treated both eyes, just out of contrast, and you can see when you treat the eyes, both of them have a very nice response to the different wave lengths, and similarly, when you oscillate both treated eyes, now just one. So again, these photoreceptor progenitors are having a very significant neural protective effect.
17. We also are finding now, and we have some work that will be published soon, that will show that they not only have a neural protective effect, but you can actually as I showed you in the RD1 mouse, actually have blind animals. We are going in with these and actually connecting up where there were no photoreceptors initially.
18. So moving on to another cell type in the eye, we are also looking at ganglion progenitors, because glaucoma is an aging disease that affects millions of people so we have two different animal models we looked at, the optic nerve crush, which is physical damage to the optic nerve, and another one is glaucoma models in both mice and rats. We even put microbeads and it caused an increase in intraocular pressure and it mimics what you see in humans, and when we transplanted these photoreceptor progenitors, which we can generate in very large numbers in a very homogenous populations of cells, you see that they mature and form very nice neurites in both of these different models. So the hope is that we can use these to treat patients who have glaucoma.
19. Similarly, we are seeing that they have a survival effect on the damaged ganglion cells, so here you are seeing actually a cross section here in an untreated animal. You are seeing the blue are the remaining ganglion cells; they are almost all missing. By contrast, when you transplant some of the photoreceptor progenitors, you see the survival, and then on the spot in the retina, you see very nice rescue of the ganglion cells. You can also carry out what is know as a scotopic threshold test and this is one of the best measures we have for evaluation of ganglion function and we can see that we get a very nice response in these animals after they have been treated with the ganglion progenitors.
20. We are also looking at other cell types, so as I mentioned those were studies that were carried out in the eye, because it is an immune privileged site, but also mesenchymal stem cells are unique in that they are also immune modulatory, so you can transplant those without immunosuppression. MSCs, as you probably know, can be found in bone marrow, adipose and umbilical cords, and they differentiate into a number of different cell types, but importantly, they exert immunosuppressed effects and they facilitate tissue repair. We have actually figured out to derive these from a hemangioblast into media, and we call these cells hemangio-derived mesenchymal cells, which for short are hMCs. Obviously this is coming from an unlimited starting source of embryonic stem cells. They are very easy to derive in large numbers. In fact, we can derive these 4 to 5 orders of magnitude in greater expansion than for instance the gold standard, which is bone marrow-derived MSCs. We have shown that they are immune modulatory, so you don't need immunosuppression when you use these in patients. They only exist transiently so they exert their effects and you don't have to worry about tumorigenicity in the long term. We have shown that this is a very strong _____ platform technology. We have actually now treated six different indications using these cells. There are a number of reasons we believe that these may be more potent than the usual cells that they used in clinical trials. Not only do they have better migratory properties than say cord blood or bone marrow blood, but they also have reduced levels of certain inflammatory cytokines such as interleukin-6 and because they are coming from a pluripotent stem cell source, you can create unlimited numbers that are nonvariable under GMP conditions from these cells. They express a variety of immune modulatory and antiinflammatory activities. For instance, you can show that the cytokines are up regulated, that modulate the behavior of different immune cells. In this particular case, hem oxygenase is up regulated. That is a potent antiinflammatory effect. Also there are other antiinflammatory agents that are secreted in response to these cells. These cells enhance regulatory T cells and they inhibit T cell proliferation.
21. This is a study we recently carried out with researcher Dr. Wang, at the University of Connecticut, here, and the paper was published last year. In this case, we were working with an experimental autoimmune encephalitis model, which very closely mirrors multiple sclerosis. What we found is that basically what happens in this model is as multiple sclerosis develops, the animals become paralyzed so at 0, that's a completely normal animal that is moving around like a normal mouse. At 2, the animal is dragging its limbs, and by the time it is up to 4, it is completely paralyzed. What we showed is that if you don't treat the animals, the animals are paralyzed, and here you see one of the animals that is untreated, which was staying there. By contrast, if you give a single injection of our cells, the animal is moving around quite normally and this, on the table here, shows you what happened. So here is the control animal. If you treat with the bone marrow derived MSCs, you get a slight response, but again, the animals still remained paralyzed like this animal there. By contrast, with our hMCs, you can see that the animals are not paralyzed. You can even irradiate these cells before you transplant them and they still reversed or prevent the onset of this disease.
22. If you look at what is going on histologically, you can see the MSC derived from the embryonic stem cells, but not the ones from the bone marrow preventing myelination of the central nervous system, so here you are seeing demyelination in these animals, and even with the bone marrow, you can see in blue that there is still quite a bit of the myelination, but by contrast, with the ES-derived MSCs, you can see quite a difference in the two groups, and we think one of the reasons for this is something known as extravasation, so if you use the bone marrow MSCs, what you are actually seeing is they get to the central nervous system, but they seem to get trapped here in the vessels and the human cells are there stained in green, FDG positive, so they are not getting out of the vessels and into the tissue to repair it. By contrast, the ES-derived MSCs, you can see that they have extravasated, they have migrated out into the damaged tissue where they can exert their effects, and we have confirmed this by looking at a number of different proteins that are involved in extravasation.
23. We have also looked at some other animal models. We looked at an experimental model of uveitis. Uveitis is an autoimmune inflammatory disease of the uvea and it accounts for about 10% of blindness in the United States, so we can again, like we do with our patients, we can look in the eyes of these animals and get an idea of what is going on in real time. In a mild model, you can see this inflammatory infiltrate that occurs and with the use of our MSCs that we derive from the embryonic stem cells, we were able to eliminate that. We repeated that with a severe model of uveitis, and again, what you are seeing here is a severe host infiltrate into the eye. By contrast, with an injection of our MSCs, you can see that process has been eliminated and this is just a quantitation of that and you can see dramatic decrease in the number of lesions with treatment of these MSCs.
24. So these can be used for a wide range of a lot of immune disease in humans. There are 100 different autoimmune diseases, one that is an important one is lupus. You may know some people who have it. It's a systemic autoimmune disease that can affect virtually any organ in the body. At least 300,000 people up to a million and a half in the United States have this disease. There is no cure, and nothing has been approved for this for many, many years. About 50% of lupus patients develop what's known as lupus nephritis and you can actually see what is occurring. If you look at the kidney, the glomeruli, this is a healthy glomeruli, and then with lupus you can see the deposition of these immune complexes, and that leads to kidney failure. We can actually study that in this mouse model, this NCDWZD mice, they just spontaneously get this lupus and in the untreated animals, you can see here in red, the animals start to die from kidney failure quite precipitously, but a single injection of these MSCs, or two injections of the smaller number here, you can see that it prevents the death of the animals, and more importantly, it actually is preventing the damage to the kidneys, so when the kidney gets damaged, you start to see protein in the urine and that is called proteinuria. So in the untreated animals, this is the degree of proteinuria, but in the animals who had 500K, two doses of these MSCs, you can see that brought that down to a very, very low level. So very significant impact on the pathology of the kidneys, and you look at BUN, creatinine and all and you are seeing similar reductions as a result of these MSCs.
25. You may be thinking, this is great, it works in mice, but will it work in humans. There was recently a study that was carried out by Walker Simon's group where they had 40 patients that were treated that had refractory lupus and they were given MSCs that were derived from umbilical cord cells. About 60% of those patients had a major ____ clinical response. In an earlier study, they actually also had a profound therapeutic effect, with long-term improvement in the disease activity, renal function and antibody levels. So you would expect from a pluripotent stem cell source like this, where the cells have stronger effect on a multitude of different immune modulatory parameters, that we would probably have even a greater impact.
26. We also took a look to see whether or not these MSCs could affect pain. So this is an ____ pain model, and what you actually have is the mouse has to push its nose through the snout to get the milk, and you can heat those bars up so as you elevate the temperature of the bars, without any analgesic, you can see that the animal stops licking, so these little bars represent each time the mouse licks. By contrast, if you give the mouse analgesic for the pain, you can see that the animal continues to lick. So it's a nice objective way to test for pain. So we looked at how chemotherapeutic agents that cause for instance ____, that causes neuropathy or capsicin, which can induce neurogenic inflammatory pain, so in this model, what you are seeing here is the untreated animals. You see that as time goes on that they stop licking. This is due to the pain. By contrast, when you given the animals the MSCs, you can see that there is no reduction in the number of licks. Similarly, if you do this study with the capsicin, you can see without the treatment with the MSCs, the animals are experiencing pain and they stop licking. In contrast with the MSCs, you can see they are not experiencing the pain.
27. We also just recently carried out a pilot study in animals that had severe Alzheimer's disease and what we found is that these MSCs had a dramatically reduced deposition of beta amyloid in the cerebral cortex of these animals, so what you are seeing here, these are the plaques in untreated animals, by contrast to the animals that were treated with the MSCs. These were treated systemically, not even intrathecally. So this is quantitating. You can see a picture, there is some reduction in the number of plaques, and similarly there was a significant reduction in microgliosis. So the next stage is to see whether or not we can actually impact the memory of their function.
28. I alluded to some of the differences that we are seeing in these cells, so if you compare the ES derived MSCs to the bone marrow and cord blood, you see that they have the lowest expression of this pro-inflammatory interleukin-6, which is very important for progression of diseases like multiple sclerosis. They also have higher expression of extrasoluable matrix to grading enzymes, which are important for them to get to where they need to get in the damaged tissue, and if you want to look at how fast they can migrate, you can actually peel some of the cells away and watch whether the cells can migrate so here is x0 to 6 hours, you can see the cells are migrating into that area. By contrast, the MSCs that were derived from the umbilical cord or bone marrow, you can see these are not migrating very much at all. So we think this is really a combination of lower inflammatory cytokine expression and better migratory capacity through the extrasoluable matrix.
29. Just to mention, there are also a lot of other potential pluripotent stem cell therapies. This is just one example. We have derived these from hemangioblasts that can be used for vascular repair. We can label these by potential cells that can become either immune cells or endothelial cells for vasculature, and if you label them with GFP, you can actually see within 24 to 48 hours, they actually go to injured vasculature. In this case it was ischemia reperfusion injury to the retinal vasculature. You exert pressure and you can see that in the untreated eyes, there is no incorporation of these cells. They're smart and they know where to go and to home to the damaged tissue. Similarly, we carried out studies in animals that had ischemic limbs, so if you look at the Doppler of the hind portion of the mice, this is the tail and this is the blood flow to the limbs, you can see this limb had ischemia to one of the limbs. One injection of the hemagio-labeled hemangioblasts and you can see within a month complete restoration of the blood flow. Similarly, in an animal with a severe myocardial infarct, you can see that we were able to cut the mortality rate in half. This is the sham versus the hemangioblasts.
30. This is just showing you that these cells again can turn into vasculature. This is a capillary structure. The cells uptake LDL, and they also turn into a variety of other hematopoietic cell types, so for instance we can turn them into entire tubes of red blood cells that transport oxygen, just like normal transfusible blood. We can also get the cells to enucleate, which is very important. We have recently generated an IPS line from O negative for an O negative individual so that the blood that we generate is now universal blood, so that means that we can transfuse that blood into virtually everyone in this room, so we wouldn't need to type the blood.
31. Also, as you know there is a serious shortage of platelets due to trauma, if you get in an accident. This is an ideal early candidate for clinical translation because platelets do not have any nucleus, so you don't have to worry about tumorigenicity, and one of the problems right now, if you generate platelets, they only survive a few days to 5 days, so that is why there is a shortage, because the cells cannot be preserved. What we are able to do is to turn whether IPS cells or embryonic stem cells, into these what's called megakaryocytes. These are multinucleated cells that then send out these pro platelet structures here, that then cleave off to become the platelets. And we find that these platelets that were generate, we can generate these in very, very large numbers, actually can form clots very nicely. They also incorporate into a mouse thrombus that was due to damage of arterial injuries with a laser. If you look at the structure of these platelets, say for instance the platelet here that was generated from IPS cell versus a normal platelet, you can see that they are virtually identical, they have this dense tubular system. These alpha granules and all the various other micro organelles, the mitochondria for example. So the hope is that the platelets will also be able to translate pretty soon into the clinic.
32. So this is just the tip of the iceberg. As you can see there are a lot of different pluripotent stem cell therapies that we hope are going to be moving into the clinic in the coming years.
33.Finally I want to thank the people who did all of the work, plus there's a team at ACT. In particular I'd like to thank Shishang Lu and Erin Kimbrel, and of course I'd like to very much thank all our academic collaborators at UConn, UCLA, Harvard, and Tufts.
34. Q: It's wonderful Bob to hear the progress towards the clinic, but you mentioned that the eye is an immune privileged site and you don't have to worry about some of the immune rejection which can happen for other tissues, in other organs. So I was wondering about your thoughts about IPS versus embryonic stem cell for those kinds of transplants, look into the future. What do you think is going to be the cell type, and can we make a new IPS cell line for every patient we treat, those kinds of issues?
35. Lanza: That is an extremely important question. What she was mentioning is going into an immune privileged site is one thing where you can go in with allogeneic cells and not have to worry so much about rejection, but as soon as you go out of these immune privileged sites, how are you going to transplant these cells, this is of course why you reject the tissue. With IPS cells of course, you can make patient-specific cells that are genetically matched to the patient so that's one way you can move to treat virtually all the other different ____, but that is going to be very expensive and very labor intensive, so another way to bypass that, which I think is the more likely way this is going to happen, is to create HLA matching banks. So in the United States for instance, 100 lines you generate would give you a complete HLA haplotype match over the majority of the patients, with 50% of the population, and other countries such as Japan or Korea, even a handful of lines would probably do the trick.
36. Q: Very exciting talk. You mentioned the RPE photoreceptors so they could enhance the eye function. So I'm wondering whether the RPE photoreceptors they encourage or enhance the survival of the host RPE photoreceptor, or directly they perform the eye function.
37. Lanza: Very good question, yes so the initial studies we had, it was very clear that when we went into say like the ____ mouse and actually in the RCS rat, you could give a ____ main injection. You're getting very nice neural protection. You can actually see the outer nucleated layer, it was very nicely preserved in the untreated animals, the outer nucleated layer was virtually gone. You do PCR on that you will see no human tissue in the eye whatsoever, so it is exerting an exocrine her paracrine function distally. So in that case we know is a very, very strong neuroprotector effect because there are no cells in the eye. By contrast, in the RD1 mice, when we put them in the subretinal space, you can actually see them migrating and actually do the ____ staining and actually see that they are actually maturing and connecting up with the existing architecture of the eye, so they have this dual ability to exert a neuroprotector effect as well as to connect up and create new photoreceptors.
38. Q: If you inject the eMSC into the eye model, could you also see signal effect, or ____?
39. Lanza: Exactly, that's an interesting question. We went on and obviously for uveitis we saw very potent antiinflammatory effect, so you could very well see an effect if you use the MSCs for other disorders in the eye.
40 Q: Thank you Dr. Lanza. I have a question pertaining to the total number of patients that have been treated or injected for AMD and SMD and the 2a patients, if you could speak to the results that you are seeing, the total number that have been injected and when you expect to go into Phase II and III.
41. Lanza: Okay, so we have treated 38 patients total in our clinical trials. There have also been 4 or 5 that were treated in Korea independently with their cells and that data will be published soon. So in total, about 43 patients have been treated with ES derived RPE cells. We're hoping in the coming months to certainly initiate our Phase II clinical trial.
http://investorstemcell.com/forum/ocata-main-forum-general-topics-science-prs-media-etc/50602-2.htm
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