Tuesday, May 26, 2015

Mesenchymal Stromal Cell Results From a Phase-I Trial

Mesenchymal Stromal Cells (MSC) are the stem cells in your bone marrow.  Stems cells can grow into beta cells, and some researchers think they can modulate the immune system (they generate one or more chemicals that cause the immune system to stop attacking beta cells).  So it's possible that stem cells might resolve both cure issues at once.  They might be able to regenerate beta cells and stop the autoimmune attack.  That is what these researchers hope.

Results From a Phase-I Trial

These researchers, at Uppsala University Hospital in Sweden, ran a phase-I trial, randomized and with a control group, but not blinded.  There were 10 people in the treated group, and 10 in the control group.  MSCs were harvested from a patient, treated externally, and then put back in that same patient.  No immunosuppression was used, and I don't think the people were ever hospitalized (the work was done in a clinic).  Data was collected on insulin usage, A1c, fasting C-peptide, and post meal C-peptide, among other measures.

Fasting C-peptide measures how much insulin your body is generating as background. It's measured while fasting, usually first thing in the morning.  This is your natural basal insulin. Post meal C-peptide measures how much insulin your body is generating in response to carbohydrates.  It's measured after eating a meal with a known carbohydrate content. This is a body's natural insulin bolus.

My summary of the results are as follows. In all cases the paper is comparing data measured 10 weeks after the treatment (which the paper considers starting or baseline data) to data measured 1 year after treatment (which the paper considers resulting data):
  1. Fasting C-peptide, A1c, and insulin usage did not significantly change for either group, and there was no significant differences between the groups.
  2. Post meal C-peptide levels for the untreated group dropped about 12%.  Dropping is bad, but it's also normal during the honeymoon phase.  In the treated group, C-peptide numbers rose 5-10%, and that represents improvement.  The difference between the two groups was statistically significant.
  3. There were no safety issues.
Discussion and Opinions

Confirming that the procedure was safe is a good thing, of course, and is the official goal of a phase-I trial.  But this is a procedure that's been done for decades to treat other diseases (especially cancer), so no surprise that it is safe.

I was a little surprised at how consistent the insulin usage, A1c numbers, and fasting C-peptide numbers were.  I assumed that A1c would still be high from diagnosis and would drop, and that insulin usage would rise to the end of the honeymoon, and that fasting C-peptide would drop.  None of that happened during the course of the honeymoon.

The important results are the post meal C-peptides.  For this data, higher numbers are good, because they mean the body is generating more of it's own insulin.  In untreated people those numbers dropped about 15%, which is normal for the first year after diagnosis.  The treated people saw a rise in their C-peptide.  There is no doubt that is good news, but it did not have an impact on the treated people. Specifically, they were still injecting the same amount of insulin, and their A1Cs did not improve.  So it's a small effect.

My memory is that I've seen this level of result several times, for several different drugs, over the last two years or so.  I think I was much more excited about them in the past.  Part of my lack of excitement is that the treatments with these results that I saw a few years ago have not progressed. They don't give better results in more recent studies.  That might be because the research is taking longer than expected, or it might be that getting a small result is much easier than getting a useful (to patients) result.  But in any case: I haven't seen forward progress in other treatments with similar initial results, so I've become less excited about these kinds of results, in general.

So in general, these results go in my "good start, but more is needed" category of results.

This study was published on line Sept-2014 and on paper in Jan-2015:

Clinical trial record: https://clinicaltrials.gov/ct2/show/NCT01068951

Joshua Levy
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.


Kathy said...

I'm very excited about this. Those C-peptide results are significant to me. As I watched my own C-peptide numbers decreasing as I was losing my islet cell transplant, I was consistently surprised at how much a difference having just a little biological help made in managing my diabetes. Even at 0.6 C-peptide, I was having far fewer and much less intense lows compared to my experiences now with no C-peptide. I envision that biological insulin knows when to back off when its not needed as opposed to the injected insulin thats there regardless.

Mitcheal Clerk said...

Thankfulness to my dad who informed me relating to this blog, this website is really amazing.checklink