Sunday, January 17, 2021

PIpepTolDC Starts A Phase-I Clinical Trial

The idea behind this research is to remove dendritic cells from a person with T1D, grow them out with vitamin D3 and a fragment of proinsulin (C19-A3), and then put them back into the same person they came from.  The goal of this therapy is to teach the immune system to stop attacking the beta cells.

Proinsulin is a molecule that the body makes as part of the process of making insulin.  The body makes proinsulin first, and then (near the end of the process), coverts the proinsulin to insulin.  Proinsulin is  a target of the immune system's mistaken attack on beta cells, so teaching the immune system that proinsulin is a normal part of the body might cure (or help to cure) T1D.

Dendritic cells are part of the immune system which find foreign cells and "present" them to T-cells (another part of the immune system) so that the T-cells know what to attack.  You can read more about them here:

Although this research is unique, it combines two parts which have each been used before.  Modifying dendritic cells has been done in the past by Trucco (late 2000s)  and DiaVacs (early 2010s).  Both groups were removing dendritic cells, treating/growing them, and then putting them back, just as done here.  The difference between all these lines of research was how the cells were treated while they were being grown outside the body.

Similarly, proinsulin (C19-A3) has been a focus of research by a group at Cardiff for over 10 years.  However,  they are testing a direct injection of proinsulin, not using it to train dendritic cells outside the body, as done here.

The Study

This is a phase-I study, enrolling 7 people, all of whom will get treated.  There is no control group.  The seven patients will be adults who were diagnosed between 1 and 4 years previously, so these are not honeymooners, they have established type-1 diabetes.  Each patient will receive two doses of the expanded dentritic cells, a month apart, and then be followed for two years.

The study has a total of five primary end points.  Some of these are safety related, and others measure the effects of the treatment (ie. how it effects the immune system).  There are also nine secondary end points, which measure effectiveness and more effects in the immune system.

This study is recruiting now and they hope to finish by October 10, 2022.  They are recruiting here:

City of Hope Medical Center, Duarte, California, United States, 91010
Contact: Ryotaro Nakamura    866-444-7538   

This study is being funded by The Wanek Family Project.


The researchers describe this as a "vaccine" or a "reverse vaccine", but most people would not consider it a vaccine at all.  Calling it a "reverse vaccine" is closer to how most people would think of this treatment.  A classic vaccine preps the body to fight off a disease.  It teaches the body about the disease ahead of time, so the body can stage a strong battle at the first sign of infection.  This treatment does the opposite.  It teaches the body not to attack something.  In some ways, it is similar to shots people sometimes get to lessen allergies.  (Although I want to emphasize that T1D is not a classic allergy.)  But in any case, I think it is a mistake to think of this as being like a classic vaccine.

Although this is a phase-I trial, it is not the first time this treatment has been tested.  It was previously tested in Europe.  This study gave three different doses to three people each (no control group).  Safety and feasibility data was good, but no effectiveness results were seen.  You can read the journal article here:


Clinical Trial Registry:

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.

Saturday, January 9, 2021

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

Beta Cells Which Hide From The Immune System

This has not progressed to clinical trials, but it is a new approach.  There is a lot of ongoing research into creating beta cells which will generate insulin in response to blood glucose, and many people talk about these as though they were a cure.  But they aren't, at least not by themselves, and for two reasons.  First, as a foreign cell they are properly attacked by the immune system.  Second, type-1 diabetes is caused by the immune system improperly attacking beta cells.  So there are two reasons why the T1D immune system is going to attack and destroy these cells.

However, the Salk Institute has found a recipe which takes stem cells and creates functional beta cells which are invisible to the immune system.  They call them "Immune-evasive".  In theory, this could protect the cells from both kinds of immune system attack, and these cells could, by themselves, cure type-1 diabetes.

Obviously, I'm going to be very interested in the research when/if it moves to human trials.  The press release from Salk makes it clear that these cells are not even ready for human trials, yet.  They need to undergo another round of animal testing, and then they can start the 10-15 years of human trials required for approval.
This is exactly the kind of research where human trials are important.  They are trying to create human cells which are hidden from the human immune system, but they must work in mice to start with.  So they are working with a specific kind of mouse called a NOD/SCID mouse.  The NOD refers to mice which have autoimmune diabetes.  NOD mice are the standard mice used to research cures to T1D.  The additional "SCID" refers to mice in which it is possible to experiment with human cells, because their immune systems have been modified to allow it.  So NOD/SCID mice are quite different than NOD mice.  That is a two edged sword.  The researchers must do it, because they can't start out experimenting on people, and yet they need to create human cells.  But SCID is a big change to the mouse immune system, changing three basic types of immune cells.  So this research is not going from mice to humans, it is going from highly modified mice to humans.  For me, this is an even larger jump, so the first human results are even more important. 


No Results from A Phase-I Trial of Ustekinumab

In 2014 a Phase-I clinical trial started to test Ustekinumab on people with honeymoon type-1 diabetes.  They completed enrollment  on May 24, 2016, which means they should have finished gathering data by May 24, 2017 and published results by May 2018.  Successful results are usually published in less than a year after completion.  But now it is well past May 2020, and I can not find any results from the study.
From my point of view, this means the study was unsuccessful.

You can read my previous blogging on this treatment here:
I think there have been a total of  three studies done on Ustekinumab, but only one is still active.  That one is in the UK and expected to finish in Oct-2022.  You can read more about it here:


Reminder: Once Weekly Basal Insulin Under Development

This is not a cure, but I'm sure some people will find it interesting.  Novo Nordisk has finished phase-II trials on an insulin that you use once a week to cover your basal needs.  You still need to take insulin for meals, but it replaces daily (or twice a day) basal insulin injections with just one injection a week.  It is called Insulin Icodec, and still needs to go through phase-III clinical trials before it is approved for use.

Fun Web Article on the History of Clinical Trials

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.