LCT's Research

Someone asked me (in personal email) to give a summary of LCT's research [r1] in much the same way I summarized Faustman's research. Unfortunately, I just don't have the time to do that detailed a job. That Faustman post took me hours of research to put together. However, here is a summary of LCT's research, but with fewer details and fewer references. I'm sorry that I can't put more time into it.

The Pre-History of LCT's Research

In the 1970s and 1980s, it was commonly thought that type-1 diabetic's beta cells had been destroyed, and if they could just be replaced, their diabetes would be cured! This led to several attempts a cures, especially whole pancreas transplants, beta cell transplants, and drug treatments designed to get beta cells to regrow (such as human growth hormone). Of course, none of these worked very well, because the body's immunology attack on itself simply killed off the new beta cells. (Although if you gave immune suppressing drugs, you could get it to work a little bit, and you needed those drugs to prevent organ rejection of the new tissue, anyway.) This whole area of transplants is still being pursued, but it is no where near as successful as it was hoped to be decades ago.

When it became clear that the body's immunology attack kept going, some researchers tried the following approach: they encapsulated beta cells inside a wrapper and then implanted the bundle it in a person. The wrapper would need to be a very high-tech material that would allow nutrients and oxygen to flow in, and wastes to flow out, and insulin to flow out, and the chemicals which triggered insulin production to flow in. But if they succeeded, it would be like having a natural pancreas inside you, but protected from the immune system.

It's a great solution if you can do it, but very hard to do. In the last 20 years or so, there have been at least half a dozen companies that have tired this. Many have gone through several bankruptcies, name changes, and purchases by other companies. So far, none have been successful. In general, these companies try solutions from a "Chinese menu" one from column A and one from column B. Column A is the material inside the wrapper. The source of insulin. Column A has things like "human beta cells from cadavers", "human beta cells from live doners", "pig cells", "cloned embryonic stem cells", "cloned adult stem cells", etc. Column B is the wrapper material. Almost every company in this area has developed their own wrapper, and they all claim their wrapper is the best (and most of them try to incorporate good ideas from other's work, as much as they can).

One of these companies is LCT [r2]. From column A they selected pig beta cells, but from a special population of pigs that had lived for decades without contact with any other mammals on an island in the middle of nowhere. From column B they developed their own wrapper technology.

LCT's Research in the late 1990s
By the mid 1990s, LCT was ready to start human trials. These trials were underway in about 1998 when disaster struck. The disaster had nothing to do with their experiment. It had to do with the British food supply. Really! Mad cow disease hit, and it was caused by a previously unknown class of organisms called prions, which can be passed from animals to humans. Since LCT's work was basically transplanting pig tissue to humans, there was some concern about this, especially since at the time, there was no testing for prions either in the pigs or in the tissues being transplanted.

New Zealand reacted to all this by stopping the LCT phase-I clinical trial immediately. So LCT's most important task became to get their clinical trials started again.

LCT's Research in the 2000s
LCT then did several studies to show the safety of their technique. They showed that their pigs did not have a prion disease, that they were not likely to get a prion disease, that the technique was not likely to transfer it to people. that no one had ever gotten a prion disease from pigs, etc. Also, they improved their encapsulation technique. But all this was to no avail. New Zealand would not authorize any clinical trials. [d1]

This caused a lot of delay, and eventually LCT decided to run a phase-I trial in Russia (see below).

Meanwhile, almost all of the other companies working with encapsulated beta cells went out of business, or abandoned that line of research. In particular, pig cells turned out to be a better line of research than human cells (and that include all types of stem cells). Some companies that had been trying to use human beta cells (of various types) tried to switch to pig cells, when it became obvious that pig cells were working better, but this just emphasized the fact that LCT was way ahead of them, since they had always been using pig cells.

LCT's Current Clinical Trials
LCT ran their phase-I clinical trial in Russia. They hired an American company to oversee it and make sure that it was up to US FDA standards, but the trial was run in Russia.

They were going to just implant about 4 people in Russia (and about 4 more in New Zealand), but when they could not get approval in NZ, they did 2 extra people in Russia. One with a higher dose of islet cells. The results of this phase-I test in Russia were pretty good [r3]:

1 (out of 6) patients went 5 months without needing to inject insulin, but then needed to restart
4 patients required much less insulin before the treatment than after (some 40% less, some 20% etc.)
1 patient was not successful, requiring more insulin after the transplant, than before it

At about the same time, LCT released results of testing one of the people involved in their mid-1990s clinical trial [r4]. Basically, what they found from that exercise, is that the implanted cells were still there and still working (at least a little). But there was no way to know if this person's implants (now 10+ years old) were generating enough insulin to have any real effect on his BG, A1C, or insulin requirements. Even so, this was good news.

The most recent news from LCT is two fold: they have finally gotten permission to run a clinical trial in New Zealand [r6], and are working tords getting approval for a clinical trial in Denver (USA) [r5]. The New Zealand clinical trial they are about to start they are calling a phase-II trial. This makes sense, since it is after the Russian phase-I trial, but it doesn't make sense from a headcount point of view. They are only enrolling 8 people, so that is phase-I sized. I don't know if they will up the dose from their earlier trial; I certainly hope so.

I don't have a reference in front of me, but I thought that the Denver trial was going to be a standard phase-II trial: 50-100 people, etc. However, since they are calling their NZ trial a phase-II, maybe they will call this one a phase-III or add more people to it? I don't know.

The Future of LCT's Research
LCT has some really good results, but they are based on less than 8 people, and only about 6 months of treatment. So the future of their research needs to show better results, for longer periods of time, on more people.

Show better results: This is what I worry about the least. Most of the people in their phase-I trial were given the absolute minimum dose of new islets, and yet they had large drops in their insulin needs. One person used no insulin for a period of time! Since actual transplants can use 2x, 4x, or many more times the number of islets, I think it is very reasonable to assume that higher doses will result in less insulin needed. In many cases, no insulin needed.

For longer periods of time: For me, this is the biggest worry. How long will these new islets last? Or, how often will they need to be replaced? There are two potential problems here. The first is that islet cells may have natural lifespans, which cause them to stop working after a certain number of years. There has been some research suggesting this (sorry: no references for this), but the exact lifespan is not known. Secondly, and more importantly, the encapsulation or transplantation of the cells may cause them to start to die off. This could kill of the transplanted islets much more quickly. For example, if the wrapper is not "good enough" islet cells may start to run out of oxygen, and very slowly die off over weeks or months. This has been a very real problem with other company's encapsulating technologies.

On more people: Because so few people have been given these islet transplants, there is always the possibility that there is some major problem that we just don't know about, because not enough people have gotten the transplant. I don't think that is very likely, but as more people are treated, we'll develop more certainty that it is safe.

My Opinion of this Research
My personal option of this research is mixed. I think that it is very likely to work, eventually. But I'm not sure how long it will take for them to tweak out all the problems. Also, it requires surgery. And I suspect that the early people to get it may need follow up surgeries every 5 or 10 years. On the other hand, I think that there are lots of people who, if you tell them "we can cure diabetes for 10 years for $50k and a three day hospital stay", many will do it. And that is a very reasonable goal for this technology within the next 5 to 10 years. And in 10 or more years, it may be cheaper or last longer, or both.

If you want to follow LCT, I recommend their web site: http://www.lctglobal.com/, which is very glossy.

There is another source, which I recommend only with serious reservations, and that is http://www.islet.org/forum/wwwboard.htm. This forum is run by an LCT cheerleader. He aggressively censors people who say bad things about LCT, or ask awkward questions. (And yes: I've been banned from the group several times.) I also believe that the forum owner makes many posts under many different names, to create a sort of false consensus on how wonderful LCT is doing. I have definitely seen the list owner post under multiple different names, I'm just not sure how many of the names on the board are real, and how many are fake. My best guess is about half are fake, but I'm really not sure.

More Discussion

[d1] Obviously there is a huge political saga here, which I will not get into.

Some References

[r1] My tracking of LCT is available here: http://joshualevy.pbwiki.com/DiabetesCureReadyForHumanTrials#LivingCellTechnologiesDiabecell

[r2] LCT home web page is here: http://www.lct.com.au/

[r3] http://www.scoop.co.nz/stories/SC0803/S00061.htm
This is a news article with selected data from the first 6 months of the Russian phase-I trial.

[r4] Results of some tests on a guy who had this done 10 year previously: http://www.diabetesincontrol.com/results.php?storyarticle=4688

[r5] http://www.cwdfoundation.org/Grants2008/LCTBDC.html

[r6] Press reports on the New Zealand approval:
http://www.fiercebiotech.com/press-releases/living-cell-technologies-receives-health-ministers-approval-start-leading-edge-live-c