Rodent Studies

Moogie1947 said:

This study was done on MICE
Today's blog from Jenny Ruhl of Blood Sugar 101 fame has something significant to say about using mice as models for humans in diabetic research.
diabetesupdate.blogspot.com/
Perhaps we should be cautious here.

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Thanks for that Moogie, Jenny certainly puts the mice studies into perspective. Will post your link on the dark side of Low Carb 8) with an acknowledgement.

Regards
Graham

This subject was raised by the good Jenny Ruhl back in October 3rd 2008.
Here is a small extract:
The dreaded words: "in mice"
Not a week goes by that someone doesn't email me with a news report about some food or supplement that cures diabetes. Invariably, the punchline of this report includes the words, "In mice." Trust me, folks. after ten years of following the diabetes racket all it takes to get me to stop reading any further are those dreaded words, "in mice."

Here is a link to the actual article.
http://diabetesupdate.blogspot.com/2008 ... -mice.html

I found the comment by Dr Denise Faustman on October 24th 2008 at 8.24am quite interesting. Jenny had criticised the learned Dr Faustman and this is part of her response.
(Quote
Yes, it is indeed true that in 2001 in mice, we cured end stage diabetes. The work represented disease reversal, not just disease prevention in truly end stage diabetic animals. The pancreas regenerated after the bad T cells were removed in part with a cheap generic drug called BCG. Now almost 8 years later, there are indeed a lot of healthy happy and formerly diabetic mice around the world as researchers verify, that at least in end stage diabetic mice, we have them well treated.

We are now in human clinical trials and human diabetic blood now shows that the way we killed the bad T cells in mice, is similarly occurring in human blood. Please log onto our web site. Your presented information is not accurate and out of date.
(Endquote).....it goes on. Read the full article and other pertinent comments at the link.

Dr. Faustman is currently Director of the Immunobiology Laboratory at the Massachusetts General Hospital (MGH) and an Associate Professor of Medicine at Harvard Medical School. After completing her internship, residency, and fellowships in Internal Medicine and Endocrinology at the MGH, Dr. Faustman became an independent investigator at the MGH and Harvard Medical School in 1987. She is a member of the American Association for the Advancement of Science (AAAS) and serves as a frequent member of the Institute of Medicine in Washington, DC. Dr Faustman's honors are numerous.

In 2001, her lab reversed type 1 diabetes in mice with end stage disease, a project that is now being translated into human clinical trials. Her current research continues to focus on uncovering new treatments for type 1 diabetes, as well as searching for therapies for other autoimmune diseases, including Crohn's disease, lupus, scleroderma, rheumatoid arthritis, Sjogren's syndrome, and multiple sclerosis.

So, we might not think much of the Diabetic Mice, however it can, and is showing benefits, even if only in the research at present. One day that 'cure' might just arrive. I for one wouldn't dismiss the use of mice as being irrelevant. Perhaps dear Jenny needs to take the blinkers off ?

Further to this, this is the current position with just one laboratory. One of the many researching for our wellbeing - a possible cure for Diabetes - now wouldn't we all welcome that ? Even if they do use Mice initially ? Phase I human clinical trial investigating BCG vaccination in patients with type 1 diabetes began in January 2008.
The Faustman Lab's clinical trial is currently testing whether using Bacillus Calmette-Guérin (BCG), a generic drug that temporarily elevates TNF levels in the body, will reduce or eliminate autoimmune T cells in patients with type 1 diabetes.

The trial’s Phase I funding is complete and the trial is in progress under the direction of Denise Faustman, MD, PhD, and David Nathan, MD, director of the MGH Diabetes Center.

The trial, scheduled for completion by January 2010, will gather information on drug safety. Subsequent Phase II trials will focus on determining the optimal dose and timing of BCG administration to achieve the desired effects in type 1 diabetes. Phase I trials are aimed at proving the drug is safe.

Is that the same BCG as the horrible injection you get a s a child to immunise against TB?
Cheers, BB

banjo brunette said:

Is that the same BCG as the horrible injection you get a s a child to immunise against TB?
Cheers, BB

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It is the very same, I remember having the injection that consisted of 9 needles in one, I can still see the marks on my forearm now........

I would question the statement hat there are healthy happy non-diabetrtic mice EEIGHT YEARS LATER.
Mice don't normally live for 8 years. I've not known many live past 3 and most don't get that far.
Hana

hanadr said:

I would question the statement hat there are healthy happy non-diabetrtic mice EEIGHT YEARS LATER.
Mice don't normally live for 8 years. I've not known many live past 3 and most don't get that far.
Hana

Click to expand...

Hi Hana, I think this is what you are referring to ?

Yes, it is indeed true that in 2001 in mice, we cured end stage diabetes. The work represented disease reversal, not just disease prevention in truly end stage diabetic animals. The pancreas regenerated after the bad T cells were removed in part with a cheap generic drug called BCG. Now almost 8 years later, there are indeed a lot of healthy happy and formerly diabetic mice around the world as researchers verify, that at least in end stage diabetic mice, we have them well treated.

What it actually means is that the mice were first cured in 2001, however since then many more mice have gone through the same process and also been cured. It is not that the mice lived for 8/9 years, just that it was 8/9 years ago that they were able to cure the mice and that has continued to this day. Leading up to the Human Clinical Trial which is ongoing.

I just found this forum/thread on a google search, so sorry to just drop in without being part of the community. Here's a brief introduction. I'm the mother of a 9 year old boy with type 1 diabetes. We just launched a new parent-led effort where we identify and help fund the type 1 research that we feel has the most promise for our children. We came to the conclusion that Dr. Faustman's work is the best hope for our kids, so we're focusing on her research first. We pay for everything out-of-pocket and direct people to donate to the research institute. We have parents involved from all over the world.

Because of our group, I've done a fair bit of research into Dr. Faustman's work. In many cases, I don't think mice are the best model for human disease. But, NOD (non-obese diabetic) mice appear to be a great model and I'll need to explain a bit about Faustman's research first to show why I feel that way.

Faustman identified the T cells that cause type 1 diabetes. She has spent a lot of time and money on developing the method to isolate these cells from the blood of people with type 1 diabetes. She found that this sub-population of T cells have a defect in a pathway that is different than ordinary/healthy T cells. The defect makes them susceptible to TNF-alpha or tumor necrosis factor, a compound our immune cells release to fight off invaders. When TNF levels rise, healthy T cells aren't affected. This is the basis of the BCG drug therapy, because the BCG vaccine causes our immune systems to react very strongly and release high levels of TNF. This kills the defective T cells that cause type 1 diabetes.

Now, here's where the mice come in. Faustman found that the T cells that attack the beta cells of mice have the same defect in the pathway as human cells -- both die in the presence of TNF. The disease process is the same. Faustman has been collecting blood from humans for at least 5 years. People from all the world travel to Boston to donate. She has been studying these T cells in humans for a very long time and they have designed and built automated equipment to measure these diabetes-causing T cells. I'm not aware of anyone else doing this anywhere. This allows the lab team to make a direct measurement of the effect of a treatment very soon after, unlike using something that requires a significant lag, like A1c or insulin dose. They measure these other parameters as well, but to actually watch what is happening with the T cells that cause diabetes is a pretty incredible thing.

Faustman published a study recently in PNAS that involved blood samples from people with type 1 diabetes. The autoreactive T cells were isolated and treated with TNF. These T cells died from exposure to TNF, just like the T cells of mice. But healthy immune cells were unaffected.

Faustman has just completed the first phase of human clinical trials with BCG. The data has been sent to the statisticians and we should hear the results next year sometime once they're published. I have a lot of hope that she's on the right track, because she's followed a very methodical path and every indiction is that her approach will work.

We made a video with a brief description of her work for our website. We also have a lot of resources about her research on our research page. There are some interesting radio interviews.

http://HelpCureChildhoodDiabetes.org

I am very excited about this work and I'm very interested in hearing the results from Phase I clinical trials -- though I should point out that this phase of the clinical trials in the States is required by the agency who oversees drug registration as a safety trial, so the therapeutic doses of BCG will not be tested until Phase II -- which is what we're trying to raise money for.

Hi rella.
Welcome to the forum. Not the usual place for welcome's, but a great first post. Very informative.
It is refreshing to see a view from someone who isn't blinkered in thinking that the use of mice in research is not a valid tool. Personally I think ANY method that has shown results such as Dr Faustman and her team have found has to be worthwhile, especially if you are a Type 1.

As this post was prompted by the comments of one Jenny Ruhle posted by one of our members a little while ago, I wonder what she thinks now ? I mean she did contribute to the research according to her blog, so she must think it has some merit.......Strange how she seems to have blown with the wind since then...... :? Maybe she has a soft spot for the cuddly little mice ?

As you say the results of the first phase are due in January 2010. I hope that they will prove that it is a safe methodology and the trials will continue. I am a T2 but I can clearly see the huge benefits that this research could in the future bring to all T1's and maybe later even be a general cure for Diabetes, who knows. My view is that instead of people trying to 'rubbish' the research, they should read up on it....they might just change their opinions about the use of mice in other research areas as well ?

Extract:
Subsequent Phase II trials will focus on determining the optimal dose and timing of BCG administration to achieve the desired effects in type 1 diabetes. Phase II clinical trial, which we hope to launch upon the successful completion of the Phase I portion. The Phase II trial will involve testing BCG in greater numbers of patients with type 1 diabetes using the dose and timing we determine from the Phase I data. It will also give us more information on how effective this treatment might be, providing the information needed to launch late-stage human clinical trials (Phase III studies). We are currently screening volunteers for the Phase II trial.

Thank you again rella for your comprehensive information. Look forward to hearing more from you.

If we don't use mice,then who wants to be first with the untested experiments?
We have to start the research somewhere.

moogie.

Nobody as far as I know is distressed ? Are you ? The post after some discussion was moved to Diabetes Discussions as it was felt more people would contribute here than in the low carb area where it was originally. That is part of what moderation is about, encouraging discussion. Of course we are not all going to agree, that's life.

I am certainly not the only one who doesn't agree, that is my opinion. I didn't 'discover' anything, I just followed a trail laid by a previous poster. We have had posts from international members in this thread, they have been happy to comment on the subject. I don't consider it is out of context and neither do others, it is just a discussion which has evolved. Happens here all the time. That's what's good about this forum. ALL opinions get heard here.

The good Jenny Ruhle was brought into the topic by a previous poster, now she had mentioned this very thing before about mice and research. So I think it is a valid point to mention that too and the efforts of the good Dr Faustman and her team. Surely we all would like to see a cure for Type 1 Diabetes and the benefits that may bring in the future.......I certainly would and I'm a T2.

I hope the discussion will continue, I find it interesting and obviously others do to. I am interested in ALL research wherever it comes from and however it is funded. It all has some merit I would have thought.

Hi Cugila,

Thanks for the warm welcome -- especially in light of just jumping in a thread from nowhere.

There are many valid points about the issues of using rodents in research and trying to translate that research to humans. Before researchers started using NOD mice for type 1 diabetes, they were just removing the pancreases or killing the beta cells in normal mice. Then if they did an islet cell transplant, of course it worked. There was no underlying autoimmune process to kill them, like there is in a human with type 1 diabetes. So research was nothing more than practice at removing and transplanting islet cells and was a total failure when applied to humans. Often times, the disease process is totally different in mice and it just doesn't translate to humans.

The NOD mouse is a very lucky model, since the precise point in the same faulty pathway is the same in humans for the cell that causes type 1. But I don't think these types of fits happen all that often.

I have to get ready for work soon (other side of the ocean), but there is some really exciting work going on with type 2 diabetes as well that provides an entirely new understanding of the mechanism. This experiment used type 2 rats and I don't know enough details about the physiology of these rats to know if they fit is as nicely as a model as NOD mice and type 1. The gist of this is that type 2 is caused by C-peptide resistance. A long back story there, but this researcher is on a roll of fitting all the pieces together. Here's a quick link and I'll try to pop back in to discuss if anyone is interested.

http://www.rsc.org/Publishing/Journals/cb/Volume/2009/9/blood_cells_get_active.asp

I totally agree, Moogie. One reason that Dr. Fausman is seeking funding from the public is because it is so difficult for researchers to go against the established dogma and get funding. I found this article on cancer research some time back and the environment seems to be the same in all areas of research.

http://www.nytimes.com/2009/06/28/health/research/28cancer.html?_r=1&hp

The research in C-Peptide, both for studies relating to type 1 (seems to prevent complications) and type 2 are hard to fund. The work in type 2 is an entirely new direction from what people have believed before. Once people start coming around to this new view, maybe we'll finally have a better understanding of the cause of type 2 so we can develop treatments that actually work.

HI rella.

Thanks for that link. That seems very interesting as it is about possible treatments for Type 2 Diabetes. Will have to read them later when I have had more time to digest them properly. As a Type 2 myself I am certainly very interested in the first. Keep us informed please.

Moogie1947 said:

This study was done on MICE
Today's blog from Jenny Ruhl of Blood Sugar 101 fame has something significant to say about using mice as models for humans in diabetic research.
diabetesupdate.blogspot.com/
Perhaps we should be cautious here.

Click to expand...

Moogie, this is your original post that was posted, out of context, in the Coconut oil thread and was therefore split and made into a thread of it's own as it was of interest. I'm confused when you say that the context has not been posted.

I picked up on this research a couple month ago, with being busy at work I never got a chance to read much further. I had no idea that it was already in human trials, if its using the BCG jab surely this should be a good thing since that is already a licenced drug so all that hs to be verified in the trials is a new treatment reigime using this drug.

Or perhaps I am being overly simplistic in my understanding of medical trials (most likely)
Does anyone know what the typical timeline would be for something like this given that its a pre-existing drug?

Surely this would be something the NHS and insurance companies would jump at since it will save them a ton of money, okay the other diabetic drug manufactureres would take a huge hit but a BCG jab a few times to cure T1... count me in

This is from Dr Faustman's FAQ section.

How long will the human clinical trials take ?

We expect the clinical trials to take around 8-10 years, but this depends on many factors, such as the requirements of the Food and Drug Administration (FDA) and the availability of funding for the different phases of the trials.
(End)

So as usual it isn't going to happen overnight. At least it's a welcome development. Let's hope it has a good outcome.