Possible Cures for Type-1 in the News (August)

This blog is a collection of short updates, mostly from the ADA conference.

Diet (Macronutrients) Does not Impact T1D Risk

Macronutrients are carbohydrates, protein, fat, sugar, and fiber (things that you eat large amounts of).  This study also looked at glycemic index and glycemic load.  It did not look at micronutrients, such as vitamins and minerals (things that you eat small amounts of).  This study enrolled people who already tested positive for autoantibodies to see how long it took them to show symptoms of type-1 diabetes.  

This study covered 881 people divided into four groups by age: 1-4 years old, 5-12 y/o, 13-22 y/o, and 23 and over.  Here is the summary of their findings:

Given multiple comparisons, there was no significant association between rate of progression from IA to T1D and daily dietary intake of any macronutrients analyzed, after adjusting for [confounders]. ... Baseline dietary macronutrient intake does not appear to influence rate of T1D diagnosis in children, adolescents, or adults with IA.  

This study is strong evidence that feeding low carb, low sugar, low fat, or any other type of macronutrient based diet cannot prevent (or even delay) the onset of type-1 diabetes, at least among people who have autoantibodies.

Abstract: https://diabetes.diabetesjournals.org/content/70/Supplement_1/1116-P

Maternal C-Peptide Generation

It has been known that women with T1D often have increased levels of C-peptide when pregnant, and especially later in pregnancy. In the past this has been considered a hopeful sign that pregnancy caused beta cells to regrow (generating the C-peptide) and that perhaps research into this phenomena could lead to a way to regrow beta cells in others with T1D.

Unfortunately, a study at ADA2021 implies that beta cells are not regrowing.  Rather, the fetuses C-peptides are moving across the placenta so they are found in the mother.  To quote the abstract:

... This suggests transfer of C-peptide from fetal to maternal serum and is inconsistent with pregnancy-related β-cell regeneration.

Tweet: https://twitter.com/ClaireMeek5/status/1409028250450509824
Full Paper: https://care.diabetesjournals.org/content/early/2021/06/05/dc21-0028 

Leptin

Leptin is a hormone generated by fat cells which helps the body regulate hunger and energy use, and may regulate other body processes as well.  Back in 2011 there was hope that it might become a cure for T1D, but clinical trials were unsuccessful.  However, there is still hope that Leptin (in addition to standard insulin use) might end up helping to treat T1D by lowering insulin spikes after meals, resulting in better control.

A poster at ADA reported on a phase-I study (7 treated people, 3 in a control group).  Basically, they gave a small dose of Leptin to people with T1D who were fasting, and then cut their pump basal insulin by 50%.  The control group's blood sugar and glucagon levels went up (as expected), but the treated group's levels went down, even though they were getting less insulin.  The effect lasted less than 3 hours.  This is a good result, if you are positioning Leptin as a "take with meals" drug to lower blood sugar spikes caused by eating.  However, this is not a cure, and I don't expect to cover it in the future.

ADA 2021 had results for a 10 person study: https://www.hcplive.com/view/oral-leptin-formulation-offers-short-term-benefit-type-1-diabetes-patients
Abstract of poster: https://diabetes.diabetesjournals.org/content/70/Supplement_1/121-LB

Viacyte Update

Viacyte was in the news this summer because they released some data at ADA (American Diabetes Association) 2021 Scientific Sessions.  Unfortunately, the data they released was from one person who was part of their "PEC-Direct" study.  The PEC-Direct study still requires people to take immune suppressive drugs for the rest of their lives.  Therefore, I don't consider this to be a cure, because it swaps one drug regimen (insulin replacement) for another drug (immune suppression).  Immune suppression has serious long term side effects, possibly worse than T1D itself.  Furthermore, I don't put much stock in single person results, so their press release had two reasons for me not to get excited.

The data showed that one person's transplanted beta cells were working well 9 months after the transplant.  Her A1c was 6.6% (compared to 7.4% before the operation) and her time within range was 84% (up from 54%).  She was still injecting insulin, however.

Viacyte is also running another study called PEC-Encap.  This study will use encapsulated stem cells and so these people will not need to take immune suppressive drugs for the rest of their lives.  I do consider that a cure.  Last I heard (from the JDCA) they were hoping to have interim results from this study in the second half of 2021 (soon!)  Those are the results I care about.

JDCA update on Viacyte from early 2021: http://thejdca.org/viacyte-2021
Viacyte press release on PEC-Direct: https://viacyte.com/press-releases/viacyte-reports-compelling-preliminary-clinical-data-from-islet-cell-replacement-therapy-for-patients-with-type-1-diabetes/
Viacyte press release on PEC-Encap: https://viacyte.com/press-releases/viacyte-announces-initiation-of-phase-2-study-of-encapsulated-cell-ther-apy-for-type-1-diabetes-patients/
News coverage: https://endpts.com/after-years-of-failure-viacyte-shows-off-first-proof-of-concept-for-diabetes-stem-cell-transplants/

Viacyte is part of a long line of attempts to cure T1D by encapsulating beta cells.  This sounds easy: just wrap the implanted cells in a membrane that lets sugar and oxygen in, insulin and carbon dioxide out, and does not allow T-cells to enter).  Seems straightforward.   For all of the last 25+ years there have been companies working on this, and none has succeeded yet.  So it is clear to me that there is something more complex and difficult about this path than we currently know.  At the moment, I think there are 3 companies working on this approach that are in human trials, or close to it.

BCG News

Dr. Faustman's lab released their most recent BCG result as a poster at the ADA 2021 conference.  They reported on demethylation of signature Treg genes.  BCG (Bacillus Calmette–Guérin) is a biologic which has been given to over a billion people (in low dose) as a tuberculosis vaccine, and is also approved (in much higher doses) as a bladder cancer treatment. It is a generic drug with a very long record of safety. 

BCG was tested as a T1D cure or preventative several times in the early 2000s (including once by this same lab), and all those clinical trials were unsuccessful.  However, Dr. Faustman's continues to run clinical trials with BCG.

In my view, these results are another step in the collapse of BCG as a possible cure. When this research started 20 years ago, it was based on curing mice. Then, the first results in people (in a tiny phase-I trial) showed very small progress to a cure in people. Later, a follow on trial showed no progress to a cure in people, but maybe small progress to treatment. Now we have these results which don't show any progress to treatment, but instead are looking at demethylation, a type of gene expression change.  The particular change they report certainly does not cure T1D, and may have nothing to do with T1D at all. By itself, it does not show progress to either a cure or treatment.

Press coverage: https://www.fiercebiotech.com/research/ada-tb-vaccine-repurposed-type-1-diabetes-restores-gene-expression-key-immune-cells?fbclid=IwAR0Jhuk8gC-IjQG6qyoX7u8UYDuP00hRtjrF5TT33RVIqnG91FnR84jazmM

Poster: https://diabetes.diabetesjournals.org/content/70/Supplement_1/1142-P

 

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.

Possible Cures for Type-1 in the News (September)

Catching Up With NNC0114­-0006 (Anti IL-21)

Back in 2015 Novo-Norsk started a clinical trial into a combo treatment of NNC0114-0006 and Liraglutide (which is more commonly known as Victoza).  I ignored this trial, because I thought that NNC0114-0006 was a new form of insulin, and they were testing a treatment for type-1 diabetes. However, I have since found out that NNC0114-0006 targets IL-21 and that Liraglutide may stimulate beta cell growth.  Therefore, this combination could have the effect of stopping the autoimmune attack while at the same time regrowing beta cells, and that would be a path to a cure.

Liraglutide is approved for use in type-2 diabetes and works by increasing insulin production. Recently, experiments in mice have suggested that it works (at least partly) by helping the body grow more beta cells, and preventing the death of beta cells:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418765/

NNC0114-0006 is an anti IL-21 treatment.  IL-21 is a chemical that the immune system uses for communication, and several experiments have suggested that too much IL-21 is important to creating type-1 diabetes:
https://www.ncbi.nlm.nih.gov/pubmed/18779574
https://www.ncbi.nlm.nih.gov/pubmed/19208913
https://link.springer.com/article/10.1007/s00125-015-3509-8
(and there are many more such studies.)

So combining these two treatments provides a possible path to a cure.

The Current Study

The study that started in 2015 is a phase-II? trial (the question mark means that it is a phase-II trial, but there has never been a phase-I trial for this combination of treatments).  The basic study design is four groups: one group gets both treatments, one group gets two placebos, one group gets NNC0114-0006 and placebo, and one group gets Liraglutide and a placebo.  So they have all their bases covered. The study is large: 304 people recruited from 100+ sites all over the US and Europe.

The clinical trial record says that this study is recruiting patients.  However, when I look at the list of locations, every one is marked "Active, not recruiting", "Completed", or "Suspended", so I'm very hopeful that they have recruited all the patients that they need.  That is important, because they expect to collect data for 80 weeks.  Their target completion date is April 2019.

This is actually the fifth study of NNC0114­-0006.  You can see the list here:
https://www.clinicaltrials.gov/ct2/results?cond=&term=NNC0114%C2%AD-0006
The four previous studies were smaller (between 10 and 65 people), and were done on other autoimmune diseases: Rheumatoid Arthritis, Crohn's Disease, and Systemic Lupus Erythematosus.

Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT02443155
Other Study ID Numbers: NN9828-4150
2014-001215-39 ( EudraCT Number )
U1111-1154-7172 ( Other Identifier: WHO )
REec-2015-1768 ( Registry Identifier: Spanish registry )

Metreleptin Fails A Phase-I Trial

Back in the 2008-2010 timeframe there was some hope that Leptin would cure type-1 diabetes, and a clinical trial was started in 2010.  Then in 2015 the trial was canceled by one of the sponsors.  Finally, now in 2017 the results have been published, and the conclusions are:

Metreleptin is safe but may not be efficacious in improving glycemic control in patients with T1DM, although it reduces body weight and daily insulin dose modestly.

You can read my previous blogging here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Leptin
The abstract is here: http://care.diabetesjournals.org/content/40/5/694?etoc
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01268644

Interesting Treatment for Multiple Sclerosis

I usually do not blog on cures or treatments for other diseases.  However, MS, type-1 diabetes and several other diseases are all from the same family of "autoimmune diseases".  They are all caused by the body's immune system attacking a different organ or internal system.  So in theory, research into curing one of these diseases might help cure the others.

So with that in mind, I thought this study was interesting:
Multiple Sclerosis Therapy NKTR-358 Begins Phase 1 Clinical Trial:

Basically, this company has a treatment which causes a person to generate more Treg cells.  Since Treg cells regulate the immune system, having more of them might prevent the immune system from attacking the wrong cells.  In type-1 diabetes, we have several research programs aimed at increasing Treg counts, but usually by growing more Tregs outside the body, and then infusing them into the body (T-Rex, Stem Cell Educator, and Stem Cells of Arabia are all working on similar ideas). NKTR-358 is a treatment which (they hope) will cause the body to generate more Treg cells, itself.

Also, NKTR-358 works at least partially, by targeting the IL-2 receptor in the immune system, and this receptor is also an active target of research in type-1:
http://cureresearch4type1diabetes.blogspot.com/2016/05/general-update-on-il-2-research.html
(and the IL-2 targeted by NKTR-358 is different than the IL-21 targeted by NNC0114-0006 above.)

Company Information: http://www.nektar.com/pipeline/rd-pipeline/nktr-358
Some animal data: http://www.nektar.com/application/files/6514/9970/7031/Langowski_NKTR-358_WCI2017.pdf

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.

Possible Cures for Type-1 in the News (November)

Ustekinumab Is Fully Enrolled

Ustekinumab, an immune modulating drug, started a Phase-II? trial in July 2014.  I previously blogged about it here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Ustekinumab

They completed enrollment on May 24, 2016, which means they should finish gathering data by May 24, 2017, because they need to gather data for a year.  Successful results are usually published in less than a year after completion.

This drug was approved in the US in 2009 for treating psoriasis, which is an autoimmune disease (where the immune system self attacks skin cells rather than pancreas cells, as with type-1).  It has also been tested on multiple sclerosis, Crohn's disease, and sarcoidosis (also all autoimmune diseases).  Ustekinumab is thought to work by blocking inflammation, and specifically blocking two immune molecules called IL-12 and IL-23.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02117765

In July, A Phase-II? Verapamil Trial Was 20% Enrolled
A research group at the University of Birmingham (Alabama) is testing Verapamil on people in the honeymoon period.  The hope is that Verapamil will cause beta cells to naturally regrow.  I've previously blogged on this research here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Verapamil

They have been recruiting for over a year, but have only enrolled 12 people, out of the 52 they need. At this rate, they will not be fully enrolled within 2 years as they had hoped, and that's a problem.

The drug they are testing is already approved (and pretty widely used) for high blood pressure, so it should not be that hard to recruit for this study.  However, only adults can be recruited (per FDA rules).  Obviously, limiting recruitment to adults still in their honeymoon phase makes this process much more difficult, since most honeymooners are youth, not adults.

Terminated: Leptin by Garg at University of Texas

On June 23, 2015 a Phase-I trial of Leptin being run by Dr. Garg at the University of Texas, was cancelled.  The clinical trial record says terminated at the request of the sponsor.  Since it was being sponsored by JDRF and by Amylin (which makes Leptin), I assume that Amylin shut down the research. You can read my previous blogging here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Leptin

At one time they were going to dose 15 people, but they ended up only dosing 7.   It was a Phase-I, pilot study, so there was no control group.  The researchers do hope to publish results, and I'll blog on them when they come out.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT01268644


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.

Glucagon / Leptin type-1 "Cure" in the News

This posting discusses research which has mostly been done on mice.  Please remember that anything that cures type-1 diabetes in mice is always years away from general availability in people.  I'm posting about this because it is making a big splash in the news, so I expect to get questions about this from friends and relations. I've already gotten questions from BBs.  Here is an example of one the better news articles:
http://www.sciencedaily.com/releases/2011/01/110126161835.htm

This research is quite different from other research aimed at curing type-1.

Drs. Unger and Lee Publish a Mouse Study Explaining Why Leptin Might Cure Type-1 Diabetes (or make it asymptomatic)

History

Several months ago, these researchers published a paper showing that giving Leptin to NOD mice was in some ways better than giving them Insulin.  Mice given Leptin had much better BG control than mice given Insulin, and that many mice given Leptin did not need to take Insulin at all.
Abstract: http://www.pnas.org/content/107/11/4813.abstract
Previous blog: http://cureresearch4type1diabetes.blogspot.com/2008/09/discussion-of-recent-press-reports-of.html
Related research: http://www.pnas.org/content/107/40/17391

Just recently, these researchers also started a clinical trial of Leptin, to see if people would have the same benefit seen in NOD mice, which I've covered a little bit.  But I did not cover it aggressively, because it was not clear if it was a cure for type-1 diabetes, or just a better treatment:
http://cureresearch4type1diabetes.blogspot.com/2010/12/possible-cures-for-type-1-in-news-late.html
http://www.clinicaltrials.gov/ct2/show/NCT01268644

Now, they have published another mouse study, which describes why they think Leptin helps type-1 mice so much.   And it is clear that they think they are on to a cure mechanism for type-1 diabetes.
Abstract: http://diabetes.diabetesjournals.org/content/60/2/391
Extract of commentary: http://diabetes.diabetesjournals.org/content/60/2/377.extract

What The Current Paper Means

This paper suggests a much different mechanism for type-1 diabetes than previously believed.
First, it suggests that mice can utilize the carbs in food without producing their own insulin.  That even animals with no beta-cells to produce insulin and no injected insulin, will still live long, happy lives if they are injected with Leptin.  Insulin is not the "key that lets sugars into cells" that we have been told that it is.
Second, The high blood glucose levels that are seen in type-1 diabetics who do not take insulin are actually caused by glucagon.  And these researchers believe that glucagon (in type-1 diabetics) is incorrectly over generated by the body, triggered by a lack of insulin.

Obviously, this suggests that type-1 diabetes can be treated by preventing (or lowering) the generation of glucagon.  In fact, from a functional point of view, it may be that preventing (or restricting) the body from making glucagon results in a "cure" where the person does not need to measure carbs, inject insulin, or suffer the long term side effects of type-1 diabetes.  This could "kick off" a long discussion of what is a cure, what is not a cure, and so on.  Different people have fundamentally different definitions of a cure, and this can lead to huge arguments.  My definition of a cure (which is on my blog) is "functional".  Others think you must stop the autoimmune attack for a real cure. I don't think it is a worthwhile argument to have now, but do remember: even in the absolute best case, this research is aimed at a functional cure.

Leptin is an example of a treatment which is known to restrict glucagon generation, but there may be others.  Some research showing Leptin's impact on glucagon:
http://www.ionchannels.org/showabstract.php?pmid=19401420

As this research progresses, it will be interesting to see if Leptin used in this way effects the use of emergency glucagon injections.  My guess is that it would not, there would be so much glucagon in the injection that a Leptin dose earlier in the day would make little to no impact.  But testing would be needed to make sure of this.

Some General Discussion

One comment I got about this research is this: "They cured mice.  So what.  Happens all the time, why care about these guys."  And that's true.  When someone announces a mouse cure, they are usually 2 years away from the start of a human trial, and often never get even that far.  But these researchers are in a different situation. They are NOT announcing a mouse cure.  They announced the mouse cure a year ago.  They have already started the human trial (3 out of 15 people already have started the treatment).  What they are announcing now is research into the mechanism that is curing these mice.

But notice how many times I used the word "mouse" in the previous paragraph.  One thing to keep in the front of your mind throughout this discussion, is that people are not mice, and mice are not people.  We know that type-1 diabetes is not the same in mice as in people.  We get mice cures at a rate of several per year.  We get people cures at a rate of zero so far.  Over 100 mouse cures have NOT worked in people.  One of my serious worries about this research is that it won't work on people at all.  That it is based on something in mice that is not there in people.  The only way to allay that fear is human trials, and that is why I'm excited that these guys have already started such a trial.

Also, it is important to remember that there were two studies, with two types of mice.  The first study, which used Leptin to cure type-1 diabetes used NOD mice.  The mice in the second ("mechanism") study were not NOD mice, and did not have autoimmunity. They were given a drug that killed their beta-cells, which induces diabetes, but not the autoimmunity part. In theory, for this research, that should not matter, but I'm always nervous about researching type-1 diabetes in mice that don't have autoimmunity.

One obvious issue is that this theory assumes that insulin is NOT actually needed to get the energy from carbs.  It assumes that if glucagon is removed, a type-1 diabetic will still be able to use all the energy in the carbs eaten.  However, this goes against mainstream medical theory that has lasted for decades.  It seems a little unlikely that no one has noticed -- even after decades of research -- that type-1 diabetics can process carbs without insulin.

Another issue is that some people have had their entire pancreases removed, and those people would not generate any insulin or glucagon.  However, they do have the classic symptoms of type-1 diabetes.  That doesn't fit in with this theory.  (Thanks to CWD's LantusFiend for pointing this out.)

I sometimes get asked "do you think it will work" (about a lot of research, not just this research).  I know that question is in the back of many people's minds.  But the question is meaningless.  It doesn't matter if I think it will work, for me or anyone else.  It only matters if it actually works, and that means data from clinical trials.  Not opinions.

How do we get from here to a cure?

I don't think we can replicate the recently announced mouse experiments in people.  These experiments used specially bred "glucagon knockout" mice.   These are mice which are a specific genetic defect that turns off their glucagon system.  I don't think there are people like that walking around.  Even if there were, we would need to find people who didn't have a glucagon system and did have type-1 diabetes.  And even if such people existed, according to these researchers, their type-1 diabetes might be asymptomatic.  They wouldn't even know they had it!  So they couldn't be recruited for a study.

So back in reality, the only way to test this in people is to find a safe way to turn down the glucagon system of someone who already has type-1 diabetes.  If this theory is right, their type-1 diabetes would become asymptomatic (or maybe they would require far less insulin than they do now).  But turning off a major hormone is not something done lightly.  Hormones are very important, and a little tricky: we often don't know all the functions that one hormone has.  Researchers are often surprised that a hormone that they thought just did X, also does Y, or stops Z from happening.  So shutting it down to help with X might cause problems in Y or Z.

So, with all that as background, these researchers know that Leptin lowers glucagon generation, so giving Leptin to type-1 diabetics is an obvious clinical trial to run, and they have already started such a trial.  However, there may be other ways to limit, control, or stop glucagon generation, and it might be interesting to run other clinical trials that use other method to turn down a type-1 diabetic's glucagon system (carefully).

An obvious question is: how safe is Leptin?  The current phase-I study in type-1 diabetics is not the first trial for Leptin.  It has already completed some phase-I studies in people who have type-2 diabetes and in people who are over weight.  However, the real question is, how safe is it when used on type-1 diabetics in the dose needed for them to get the good effects we want?  And also, do any safety issues surface in the larger phase-II and phase-III studies (for any indication)?  And those issues can only be resolved by going through the clinical trial process.

Finally, Amylin is a commercial company that is researching Leptin, and they are a collaborator in the clinical trial.  Amylin is a big name in the treatment of type-2 diabetes, but as far as I know, they do not have a drug aimed at type-1 (so no "conflict of revenue").  They are interested in Leptin as a combination weight loss treatment.  But obviously, good results in treating type-1 could open up a whole new market for them.

One Last Point

If these guys are right about glucagon and Leptin in people, and their study uses the right dose, then they are going to find out quickly.  Their current study is NOT blinded, and they believe the effect is not honeymoon dependent.  So even though their experiment is supposed to last until early-2013 (and may last longer), the researchers involved (and the patients involved) may know sooner.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. 
Blog: http://cureresearch4type1diabetes.blogspot.com
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

Possible Cures for Type-1 in the News (late Nov)

Here are various news items on possible cures for type-1 diabetes which are in human trials, and related items:

Diamyd Completes Enrollment of their Second Phase-III Trial

Since this study follows people for about 15 months, it is very reasonable to expect that it will complete in mid 2012.  Since this is the second phase-III trial, if successful, market approval might come in 2013 or 2014.  Diamyd is a vaccine like treatment designed to teach the body's own immune system to stop attacking it's own beta cells.  The company's description is this: "Diamyd® is thought to induce tolerance to GAD, thereby intervening in the autoimmune attack and preserving the capacity to produce insulin in patients with autoimmune diabetes".  Remember, the phase-III trials are only in honeymoon diabetics.

Press release: http://www.marketwatch.com/story/diamyd-medical-diamyd-completes-screening-for-us-phase-iii-study-2010-11-10?reflink=MW_news_stmp

Leptin Starts a Phase-I Clinical Trial, but as Treatment, not Cure

I have blogged in the past about Leptin:
http://cureresearch4type1diabetes.blogspot.com/2010/04/possible-cures-for-type-1-in-news-april.html
http://cureresearch4type1diabetes.blogspot.com/2008/09/discussion-of-recent-press-reports-of.html

And here is the press release for the new news:
http://www.prnewswire.com/news-releases/juvenile-diabetes-research-foundation-and-amylin-pharmaceuticals-partner-to-investigate-metreleptin-as-potential-therapy-to-improve-blood-glucose-control-in-type-1-diabetes-108399354.html

Back in 2008 Leptin was presented (in the news, at least) as a possible cure, but by April 2010 it was presented as a possible new treatment.  This most recent news makes it clear that it is a possible treatment for type-1 diabetes, not a cure.  I don't expect to cover this research moving forward.  Remember that even as a treatment, it takes 10 years to move through the regulatory process and get approved.

Single case of Putting Type-1 into Remission for One Year
This is a single patient report (not a research study).  The patient had two diseases: ITS and type-1 diabetes.  To treat ITS, she was given Rituximab about 15 months after being diagnosed with type-1.  The result was that her type-1 diabetes went into remission for 11 months.  (No need for external insulin during that time).   This is reported here:  http://care.diabetesjournals.org/content/33/9/e122.full

Obviously, this is interesting.  Especially since there has already completed a phase-II study on type-1 diabetics, and got good results there, too.  (Although I'm embarrassed to say that I've not blogged on the specific results of that study.)

Rituximab targets the CD20 part of the immune system's B cells (different from the pancreas's beta cells) to try to prevent the autoimmune attack. B cells are part of the body's immune system and communicate with the T cells, which actually attack the body's  beta cells in the pancreas.  By targeting the B cells, it is hoped this treatment will stop or lower the attack of the "bad" T cells.

Comment: Most treatments aimed at stopping the autoimmune attack are very focused on stopping the "bad" T cells which directly attack the beta cells in the pancreas.  This treatment (if successful) opens up a whole 'nother way to stop the attack: by targeting the immune systems communication and support system, the B cells.

I have previously blogged on Rituximab here:
http://cureresearch4type1diabetes.blogspot.com/2009/07/update-on-pescovitzs-rituximab-phase-ii.html
And reported status here:
http://joshualevy.pbworks.com/w/page/13864073/DiabetesCureReadyForHumanTrials#RituximabbyPescovitzatIndiana

Cautionary Note: Possibly Faked Phased Clinical Trial Data
This news article made me very nervous; the impact could be to many other clinical trials. 
Here is the article:  http://www.russia-ic.com/education_science/science/science_overview/1202/

The basic summary is this:  MannKind is developing an inhaled insulin doing several clinical trials in foreign countries, using contract clinical trial companies.  (These are companies that specialize in just doing clinical trials for other companies.  They don't develop drugs.  They do testing of other company's new drugs.)  A MannKind employee claims that some of the data reported by the contract clinical trial company in Russia is obviously false.  All patients had the exact same blood pressure.   Since FDA relies on these studies to do approvals, this is a big deal.  This one case impacts MannKind, but the general problem could effect others treatments as well.  Did that contract clinical trial company do other trials for other drugs?  Is the problem limited to one company, or does Russia have systematic problems that put all Russian clinical trials at risk?  You get the picture: it's bad.

Omission from Previous Blog Entry
In my last blog (comparing Burt's treatment with LCT's) I did not include the fact that LCT's clinical trials were all people with established type-1 diabetes, while Burt's were all honeymooners (people with recent onset type-1 diabetes).  This is a serious omission.  Working on established type-1 diabetes is a huge advantage over honeymoon type-1 diabetics, and that is a strong point in LCT's favor that was not included in the comparison.  I'm sorry for this omission.
 

General Background Information

All "Animal Models" are not Equal
This is an interesting blog entry about "animal models" used to test type-1 cures:
http://www.solvingdiabetes.org/2010/10/24/animal-models-of-autoimmune-diabetes/

General Background for Understanding Type-1 Research
This article describes the immune system in general, what is meant by "honeymoon" and other useful words and ideas, but the Teplizumab clinical trial it talks about has since been stopped.  Also the phase-I/phase-II/phase-III description is for new drugs or treatment.  Already approved drugs or treatments can follow a slightly different path.
http://www.jdrftalk.org/2010/09/28/diabetes-and-autoimmunity/

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials