For over 10 years there has been a research group at Cardiff University (UK) working on creating vaccine-like treatments to cure or prevent type-1 diabetes, and this blog posting covers their recent results.
As background: one of the autoantibodies that is associated with type-1 diabetes targets insulin molecules [d1]. Therefore, there is a theory that giving people with T1D a protein fragment from insulin might prevent or delay the onset of type-1 diabetes. It would train the body not to produce this autoantibody. The process is vaguely similar to giving small amounts of peanut proteins to people with peanut allergies [d2]. These researchers are using a peptide (a small part of a protein) from proinsulin, which is a precursor of insulin.
Results From Phase-I Clinical Trial of Proinsulin Peptide Vaccine in Honeymooners
This trial involved 27 people divided into three groups. One group got a placebo and was a control group, the other two groups got the Proinsulin Peptide injections for 6 months. One group got the peptide every 2 weeks, the other every 4 weeks. The people were adult, honeymoon diabetics (within 100 days of first insulin injection). They will be followed for 3 years, although this publication only covers the first year after treatment.
The untreated group went through a normal honeymoon period, where over time they gradually generated less and less of their own insulin, and had to inject more and more. However, the treated people (on average) held steady in their ability to generate their own insulin, and did not lose their ability to generate insulin for the time covered. So this meant that the treated group did better than the untreated group over time, and the difference was statistically significant. Also, there were no safety issues.
JDRF funded this trial specifically, and this whole line of research, in general.
News Coverage:
http://www.medicalnewstoday.com/articles/318899.php
http://www.latimes.com/science/sciencenow/la-sci-sn-diabetes-immunotherapy-20170809-story.html
Abstract: http://stm.sciencemag.org/content/9/402/eaaf7779
Full Paper: http://stm.sciencemag.org/content/9/402/eaaf7779.full
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT01536431
Discussion
I think there are three important points for this research:
First, these results are good enough to spur a phase-II trial, and the Cardiff researchers have already made it clear they hope to run a phase-II trial starting in 2018. Two of the authors of this paper are consultants to UCB Pharma to help design that trial. So that is good.
These results join a growing number of treatments with what I call "medium good" results in honeymooners. "Medium good" means that the treated group did not get worse, but did not improve either. This is in comparison to the untreated group which did get worse. (During the honeymoon phase, people with type-1 diabetes get worse: they gradually lose the ability to generate insulin. They go from generating a little insulin, to generating none.) I think there are about half a dozen treatments which have phase-I or phase-II? results of this type. So it's better than nothing, but because none of these treatments have moved forward to even better results, I'm not not particularly excited about them. I'm still hoping for better results in future trials.
These "medium good" results may become even more valuable in the future, if they can be applied to people in the earliest stages of type-1 diabetes, when they have two autoantibodies, yet are not showing any other symptoms. I'm hopeful that preserving insulin generation at that level could delay or prevent needing injections completely.
Second, this same research group is working on another clinical trial closely related to this one, but it has not gotten as far along the development path: https://clinicaltrials.gov/ct2/show/NCT02837094 (This is an 8 person clinical trial without a control group.)
Finally, this same research group is working on a similar treatment, but based on many peptides, rather than just one. That trial is called MultiPepT1De:
https://clinicaltrials.gov/ct2/show/NCT02620332
They completed recruiting on 3 July 2017, so should finish gathering data about the end of 2017.
Details
[d1] Autoantibodies are the malfunctioning antibodies which cause the immune system to attack beta cells. There are five autoantibodies associated with type-1 diabetes, and there may be more that we haven't discovered yet. The five we know about are:
* micro insulin autoantibodies (mIAA or just IAA)
* islet-cell antibodies (ICA)
* glutamic acid decarboxylase (GAD) antibodies
* islet antigen-2 (IA-2) antibodies
* zinc-transporter 8 (ZnT8) autoantibodies
[d2] It is important to realize that type-1 diabetes is NOT a conventional allergy to insulin. It is similar to allergies in that it is the body's immune system overreacting to something that it should not react to, but other than that, is quite different. Allergies involve the immune system overproducing histamines. These histamines attempt to get physical irritants, like pollen, out of your body. You can counter this histamine reaction by taking antihistamines. Type-1 diabetes involves the immune system overproducing malfunctioning killer T-cells (or perhaps under producing regulatory T-cells). These malfunctioning killer T-cells mistakenly kill beta cells, thinking they are foreign cells (ie. living creatures like viruses, that have invaded the body). So the mechanism is different (histamines vs. T-cells), and the mistaken target is different (physical things, like pollen or wheat vs. living organisms, like viruses).
Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.
4 comments:
The danger with this, as with all efforts to prevent type 1 diabetes from developing or to stop its evolution in the initial phase, is that it will make those who now have an established case of the disease the 'last generation of freaks,' mere medical curiosities who will be pitied but whose condition will no longer attract any scientific research efforts since once we are gone, the disease shall have vanished, like the English Sweating Disease and similar conditions of the past. So, ironically, progress in such efforts is the last thing that should encourage us.
I agree with Oscar
Oscar, I have to disagree with you. The success of a "prevention"-type cure would open the door to a cure for all who are currently living with type 1. If the progression of type 1 autoimmunity can be stopped, transplanted islet cells from donor cells or from the lab would potentially become a long-term cure. We might see the widespread success of an Edmonton-protocol transplant cure, without the immunosupression and without the degradation of transplanted islet cells insulin production.
Well, the cells for transplant would either have to have been preserved from the patient before the patient's beta cells were destroyed, or they would have to have been made from the pluripotent stem cells of the patient, which is not an easy task. If you take them from any other source, then even if you have found a way to stop the patient's own autoimmunity from acting, you are going to have to put the patient on toxic life-long immunosuppression to combat the ordinary immune processes of the body.
There is also the problem of the extreme shortage of pancreases for transplant even now, with the very limited number of pancreas transplants which are performed. Transplanting beta cells from animal sources, which could be done if they could be encased in capsules protecting them from the immune system, would solve the shortage of material to transplant, but it could not work without encapsulation, given the hyperacute rejection which results from transplanting animal tissue into humans.
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