Friday, August 16, 2013

One Year of "Cured In Mice"


At the end of 2011 I started keeping track of all the treatments that were discovered to cure type-1 diabetes in animals.  Throughout 2012 I kept track of all these announcements, so now I have a full year's data on type-1 cures in animals, and this blog posting is a summary of that data and my thoughts on it.

You can see all these potential cures here: http://t1dcuredinmice.blogspot.com/

Summary of One Year of "Cured In Mice"

The big news is this:  Depending on how you count them, there were between 10 and 18 animal cures discovered in 2012.  That's a huge number.  Much more than I expected.

What kind of mouse cures were found?  Everything that I could imagine, and some that I couldn't imagine.  There were animal cures based on growing new beta cells in the pancreas and in other parts of the body.  There are stem cell cures, nanoparticles, parasitic infections, a natural/alternative/complimentary cure, all kinds of drugs, and biologicals.  Even "hyperbaric oxygen" made an appearance.

Here is the full list. More details (including web sites) are on the t1dcuredinmice blog.

Trial
Treatment
Animal Results
ViaCyte VC-01: encapsulated stem cells diabetic mice and rats Cure
Sheba Medical Ctr. Ad-CMV-PDX-1 CAD-NOD mice 43% Cure
Feinstein Institute ISO-1
NJ Medical School intestinal parasite NOD mice Prevention
Karolinska Institutet M2r macrophages NOD mice 65% Prevention
U British Columbia human embryonic stem cells STZ mice Beta Cell Creation
U North Carolina non-depleting antibodies NOD mice 80% honeymoon cure
U Florida Adult Stem Cells + Beta Cell Growth Factors mice Cure
DRI Hyperbaric Oxygen mice 30% Prevention
KU Leuven proinsulin autoantigen NOD mice, Honeymoon Cure
St. Jude  Hospital Interleukin-35 NOD mice
U Colorado CD40 inhibitory peptide mice Prevention and Cure
XOMA XMetA mouse model of diabetes lower A1C
Hannover Medical School Hepatic Insulin IDDM and STZ Rats Cure
Vanderbilt U Brown Fat STZ mice Cure
U of Tokushima anti-CD98hc TZ NOD mice Cure
Parvus Nanoparticle mice 70% Cure
Academia Sinica Catenarin NOD mice Prevention

Notes on Animals

NOD mice have an autoimmune diabetes similar to human type-1 diabetes.  STZ mice have had their beta cells killed with a toxin, and therefore have no autoimmunity issues.  CAD-NOD mice are NOD mice where the type-1 was triggered with a toxin.

The Allure of Animal Research

One of the themes that I repeat over and over in this blog, is that animal research -- even really successful, animal research that sounds like a great idea and a sure winner -- is always a long way away from real success in people.  Reading this paper on Catenarin:
http://www.hindawi.com/journals/ecam/2012/982396/   (especially figure 2A)
really reminded me of the dangers of the siren-song of animal research.  How easy it is to sound really good, like a cure was just around the corner, even when it is not.  This paper shows a graph where untreated animals start to come down with type-1 diabetes at 12 weeks, and by 24 weeks every animal has type-1 (100%).  They give animals the smallest dose of Catenarin, and at 24 weeks only 70% of the animals have type-1; a medium dose results in 30% type-1 diabetes rates, and at full dose, no NOD mice get type-1 diabetes.  Even at 30 weeks, none of the full dose mice have type-1.  On paper it looks like the perfect preventative.  It looks so beautiful, so alluring. There is no reason why it shouldn't work; no reason why we should fund any other research.  So perfect.  And yet, so many treatments have shown this in mice.  Most wildly successful mice treatments never even start a human trial, and most of those that do, fail.   Reality is so hard, sometimes.  This is part of the reason I don't follow animal research very closely.  Too much heart-ache.  Even with human trials, there is too much, but with animals, it is even more.

The Future

How many of these animal cures are going to progress to human clinical trials?  I don't know.  So far the answer is none, but it's only been 8-20 months, and that's not a lot of time to translate into human trials.  But this is definitely the next piece of data to gather: out of the animal cures in 2012, how many turn into human trials in 2013, in 2014, in the next 5 years, or ever?  In looking over the research, I have a sinking feeling in my stomach, that very few of these are ever going to be tried in people.  But I'm really just guessing, and the whole point of gathering the data, is so I don't have to guess.
  • The ViaCyte researchers are very specific about planning to start human trials in 2014.
  • The lead Feinstein researcher (Dr. Al-Abed) "is now designing clinical trials" according to their press release. 
  • I have heard some discussion about a human trial for the intestinal parasite tested at NJ Medical School, but there is widespread belief that very few people will volunteer for this, so there is little enthusiasm for starting the trial.
I'm not planning to continue the "Cured in Mice" blog, because I feel it has served it's purpose, and the extra work involved in keeping two blogs up to date is not worth it.  I may blog on animal research slightly more often here, but I don't think it's worth a second blog.

Joshua Levy -- Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail 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.