What is he trying to do, and what is the current status of the Research?
The basic plan is a two pronged attack [r1]: First, drugs are given to shut down (or almost shut down) the immune system. Second, the patient is given drugs to stimulate adult stem cells, which are then removed from his or her blood, treated, and reinjected into the patient. [d1]
In some ways, this research is similar to Trucco's [r7] and also Gitelman's [r6].
Gitelman is using ATG in his research, and that is one of the drugs used in Burt's research as well.
What is the good news?
The good news, is that it works. Burt's results -- in term of curing people for months and even years at a time -- are amazing. Much better than any other research that I know of. More than half of the people treated stopped requiring insulin for the entire time they were followed: a period of months, in some cases years! The rest of the people (except one) required much less insulin after the treatment than before it. That's huge, and no other treatment has come close.
To be specific, one year after treatment, of the 15 patients treated, only two were using injected insulin at the end of the first year after treatment, and 11 of the patients had never (or almost never) had to use injected insulin after the treatment [r8]. The [r1] reference also contains A1C data for these patients, which is also very good.
In a later follow up [r5] the results were also good. Out of 21 patients (and excluding one who had DKA), 13 patients were permanently free of insulin for as long as the study followed them. Some of these people were followed for more than 3 years!. 6 more patients were insulin free for some months after treatment. Just eye-balling that data, it looks to me like those 6 were insulin free for about 66% of the months after treatment. Only 2 patients from the 21 treated were never insulin free.
What is the bad news?
The bad news, is that it might be dangerous; even deadly. This treatment is quite complex. High doses of immunosuppressive drugs are given, and then different drugs are given to create stem cells, and then those are treated with other drugs. Finally, another bunch of drugs are given to lessen the severity of various side effects of the primary drugs. So there is a lot going on. In particular, the immunosuppressive drugs have serious short term and long term side effects. Some of the patients in the clinical trials were hit by some bad short term side effects of these drugs (although nothing permanent). There are also long term dangers of these drugs. In some cases, drugs in this class raise your chance of getting rare cancers even years after they were used.
Now, all of the drugs given as part of this study are approved for human use (for other treatments), but they are also well known to have dangerous side effects. In many cases, these drugs are approved to treat deadly cancers where the general tolerance for side effects, and even the chance of death is much higher than for a child with type-1 diabetes. My biggest single problem in getting excited about this research, that I don't know exactly how dangerous these drugs are, in the doses given here.
An interesting digression on "honeymoon" only clinical trials.
This study is a classic "honeymoon only" clinical trial. Only people who had been diagnosed for less than six weeks were admitted into the study. On the other hand, if a person's body can regenerate new insulin producing beta cells (as many researchers now believe), then this cure could work on established diabetics, too. Burt and his team believe that giving the immunospressive drugs early (when the body still has some working beta-cells) is important. However, if the body naturally regenerates these cells, it may turn out not to matter so much.
Some discussion of stem cell research issues.
This work uses stem cells, and it is being done in Brazil, even though it is based on research done in the US. This has led some people to jump to the conclusion that it uses embryonic stem cells, and was forced out of the US by right wing Christian objections to embryonic stem cells. However, I do not think this is what happened to this particular research. Not only are these guys using adult stem cells, they're using the patient's own stem cells. So only the most wacko religious loony is going to object to that.
On the other hand, there are other ethical issues involved in this research, which you can read about [r2,r3]. Basically, they involve using children in the initial clinical trial. There is no doubt that this trial followed all the proper legal and ethical rules for Brazil; but doing phase-I research on children when the drugs given are known to have serious side effects does raise ethical issues.
If I had more time....
If I had more time, I would certainly spend some of it researching the safety profiles of the various drugs used in this research. After all, if the drugs are safe, then this research is showing the highest cure rate of anything out there. Conversely, if the drugs are dangerous, then they will need to do a lot of research to find safer alternatives or lower doses, before I will personally be interested in this treatment.
Another project, if I had more time, would be to create a simple table comparing the most recent results of different clinical trials. For each trial include data points like: % drop in insulin use (average and standard deviation), % drop in A1C, % chance that a patient will go a month without using insulin, % chance that a patient will go a year without using insulin, etc.
If I had a spare 10 million (US$) lying around....
If I had a spare 10 million to spend, I would try duplicating this research on non-honeymoon diabetics, and I'd do it in the US. After all, since these would be people who had type-1 for years, so it could be done on adults, and so it could be done in the US.
A few random thoughts.
One interesting complexity in this research, is that it failed on the first person it was tried on. That person had DKA. After that, people who had DKA were excluded from the study, and everyone had much better results. Almost all diabetics, at some point, get DKA for some period of time. So if this is to become a widespread treatment for type-1, then the role of DKA will need to be better understood.
This sort of treatment might already be a competitor of islet cell transplant therapies. After all, those people must be on immunosuppressives for their whole lives (although at low dose). It might turn out that Burt's short term, high does treatment is overall safer than the long term, low dose that they get now.
Extra Notes and References
[d1] this is the exact quote, which I have a hard time translating into English. If anyone knows more specifically what it means, here it is, from [r1]:
Hematopoietic stem cells were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (10 µg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg).[r1] Abstract of the JAMA article published in 2007
[r4] Some results and discussion:
[r5] A different report:
[r6] Gitelmans work is described here, on my web page:
[r7] Trucco's work is described here, on my web page:
[r8] See the graphs here: