Tuesday, April 3, 2012

Encapulsated Beta Cells and Sernova

This blog contains two parts.  The first is a general update on encapsulated beta cells as a possible cure for type-1 diabetes, and the second is some background and an update specifically on Sernova corporation's work on encapsulated beta cells.

General Update on Encapsulated Beta Cells
The basic idea, is that you take working beta cells and wrap them in some kind of barrier (called "encapsulation"). It must allow nutrients and sugar to flow into the beta cells, and insulin to flow out of the beta cells, but must stop the body's immune cells from getting to the beta cells.  So it must not be a complete (impermeable) barrier, but a "smart" or partial barrier.  The beta cells generate insulin in response to blood sugar.  Because they are encapsulated, the body's own immune system can not attack them.  This means both that the body's broken autoimmune attack does not kill off these beta cells, but it also means that the body's natural attack on any transplanted organ doesn't happen either.  These are both good things.

For more background, the Dec-2011 Countdown (a JDRF Publication) has a good article on Encapsulation: http://countdown.jdrf.org/Features.aspx?id=8589934725
Obviously, it focuses on JDRF's work, but it also contains a lot of the history, complexities and past problems of using encapsulated beta cells to cure type-1.  The discussion of past problems is important.  Many people seem to assume that since encapsulation sounds like a good and simple idea, it is a good idea and simple to implement.  However, different researchers have been working on this idea for over 20 years, and a cure has not been forthcoming.  So obviously, it is not as simple as it sounds.

Below I discuss status for all the encapsulated beta cell projects that I know of.  The basic summary is that one commerical company and two academic teams are in clinical trials now:  LCT is in phase-II trials and the others are phase-I, by my standards.  Sernova hopes to start clinical trials this year, but not on encapsulation directly, and the rest are in animals trials.

Status of LCT http://www.lctglobal.com/
LCT has completed a phase-I clinical trials in Russia, and has one ongoing in New Zealand.  They have also started a third clinical trial in Argentina.  At one time, they were hoping to have commercial availability in Russia in 2011, but that did not happen.  Results in people have been mixed.  A small number of people have been cured for short periods of time, and most people see improvement in their  BG control.

Status of AZ-VUB  http://clinicaltrials.gov/ct2/show/NCT01379729
This is academic research with human beta cells.
A 10 person trial, started in 2011 ends in 2013, but then patients will be followed until 2018.

Status of Université Catholique de Louvain http://www.clinicaltrials.gov/ct2/show/NCT00790257
A 15 person trial, started in 2008 and running until 2013.

Status of Sernova http://www.sernova.com/s/Home.asp
I discuss this more below, but Sernova hopes to start phase-I clinical trials in the first half of 2012 [d1].
They have already completed large animal trials.
Recent Interview: http://aheadoftheherd.com/Newsletter/2012/Ahead-Of-The-Herd-With-Sernova.html

Status of Cerco   http://www.hanumanmedical.com/  http://www.hanumanmedicalfoundation.org/type-1-diabetes-research.html
These guys are doing large animal studies now, and hope to start human trials in 2013 [d1].

Status of ViaCyte  www.­viacyte.­com
These guys are using putting embryonic stem cells into their encapsulation, which is different than the other research teams listed here, who are mostly using pig cells.  These guys have cured mice and are doing animal safety studies now, and hope to start clinical trials in 2013 [d1].
Interview: http://www.diabetesmine.com/2012/01/whats-up-with-diabetes-stem-cell-research-firm-viacyte.html

Status of Nuvilex    Cured In Mice! Nuvilex
These guys are "cured in mice".  We'll need to see what happens in people.

Background on Sernova

Sernova has a long and interesting history, which I summarize here:

It has been known for a long time, that the body's immune system does not have complete coverage within the body.  For example, the immune system is not good at attacking viral infections in the eye (for example)[d2].  One of the things that the body's immune system does not attack is your own sperm cells (or egg cells).  If you think about it, these two cells have a different genetic makeup then your body, and they might be identified as foreign invaders and attacked by the immune system.  However, this does not happen.   For sperm cells, the body has special cells, called Sertoli cells, that  are located next to the sperm cells and prevent the immune system from attacking them. [d3]

So, long ago (about 15 years) and far away (Mexico) a transplant surgeon named Rafael A Valdes-Gonzalez decided to implant into people a mixture of Sertoli cells and beta cells from pigs.  The Sertoli cells would protect the transplanted beta cells from the body's immune system. (See [d4] for discussion on pig cells, and [d5] for discussion on ethical apprvoals.)  Dr. Valdes-Gonzalez thought he was on the track to a cure, and published some promissing results [r1], but others were not so sure [r2].  Also, the standards for exotransplantation were still being created, and no where near as well formed as now.  So there was some controversy [r3].

So, when it was time to start a larger, more carefully controlled clinical trial, to resolve the doubts about the effectiveness of the treatment, the local trial review board did not give it's approval.  They pointed out that the current standard was that animal studies (preferably large animal studies) should be done prior to human studies (to assure a basic level of safety and a reasonable chance of success).  These studies had never been done.  Dr. Valdes-Gonzalez  was a transplant surgeon who was not focused on running animal trials.  As far as I know, the Mexican project has not made a lot of forward progress since then.  However, at one time around 2004, they were "open for business" at about US $35k for the operation[r4].  I don't know what the current status is.

Obviously, a lot of people were unhappy about the lack of forward progress.  One of these people was Dr. White, a Canadian researcher.   He decided to develop the Sertoli+Beta cell treatment, starting from animal trials, and worked with Sernova corporation to do so.

Sernova is working on two related projects.  The first is a pouch system which holds transplanted cells together in one place (but does not encapsulate them, there is no barrier involved).  The second is the Sertolin(tm) system, which is designed to use Sertoli cells to prevent an immune attack on the transplated cells.

Here is a quote from their web page:
Sernova, is developing two novel closely integrated proprietary platform technologies. The first is the Cell Pouch System™, a scalable device providing a natural "organ-like" environment for therapeutic cells such as insulin producing islets for diabetics and the second is Sertolin™, a cell-based technology providing an immune-privileged environment for donor cells, reducing or eliminating the need for anti-rejection drugs.
Also, their home page includes two video presentations and a power point presentation which describe what they are trying to do.

Sernova has announced that they hope to start phase-I trials for their Cell Pouch System in the first half of 2012[d1], so that is great news.  But it is limited news.  By itself, this provides no immune barrier, so it's not even part of an eventual no-rejection drug cure.  Is just a step in that direction.  Sernova has said that they are hopeful that if the pouch is successful, it means that in the future only local immune suppressive drugs would be needed.  Because the beta cells would be limited to one specific place, immune suppressive drugs would only be needed right there, also.  Since local immune suppression is safer and has less side effects than whole body immune suppression, but there's no way to know if the difference will matter.

Extra Discussion

[d1] When I use the phrase "hope to start clinical trials in ..." that means that the company or organization has said that publicly.  It does not mean it will happen; nor does it mean that I think it will happen.  Researchers in general have a strong tenancy to think they will start human trials much sooner than they actually do.

[d2] and some researchers at DRI are experimenting with transplanting cells into the eye, specifically to take advantage of this, but no human trials as yet.

[d3] After reading this, you might ask yourself, why bother with transplanting the beta cells at all?  Why not just put Sertoli cells right next to existing beta cells, and then they would protect the beta cells from the autoimmune attack.  People are working on that:
http://t1dcuredinmice.blogspot.com/2009/10/sertoli-cells-by-fallarino-at.html
but it has not progressed to human trials, yet.

[d4] The insulin generated by pig cells does work in humans.  For decades, humans injected pig and cow insulins as standard treatment.  It is only in the last 40 years or so that we have used human insulin from genetically engineered bacteria.  Prior to that, it was all animal origin insulin.

[d5] I've read several different accounts of the ethical approvals that this research had, and what it needed.  My belief is that it did have the proper approvals from the proper authorities at the time that it started, although some have claimed that the ethical approvals were lax.

References

Here are a link to PubMed references for all of Dr. Valdes-Gonzalez's work:
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Valdes-Gonzalez%20R%22%5BAuthor%5D

[r1] The good results:
Three year follow up: http://axacell.com/uploaded/Publication%20Three%20-yers%20May%202007.pdf
Four year follow up:  http://www.eje.org/content/153/3/419.full.pdf+html
Long term follow up: http://www.ncbi.nlm.nih.gov/pubmed/20964645

[r2] I doubt this is a complete list of the doubters:
http://www.eje.org/content/154/6/917.full

[r3] This is not a complete list on the controversy, but enough to get you started:
http://www.ualberta.ca/~dcl3/Ref_2007-Aug-17/islet%20transplantation/islet_xenotransplantation_are+we+ready+for+clinical+trials.pdf
http://www.nature.com/nature/journal/v419/n6902/full/419005b.html
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)09285-1/fulltext
http://www.lancet.com/journals/lancet/article/PIIS0140-6736(02)09287-5/fulltext

[r4] http://eprints.qut.edu.au/3449/1/3449.pdf

Finally.....

I found this on the JDRF's "For Scientists" web site about encapsulation in general:
http://www.jdrf.org/files/General_Files/For_Scientists/MS2011/FY12_Encapsulation_Consortium_RFA_11.16.11.pdf


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. My blog contains a more complete non-conflict of interest statement.
My Blog: http://cureresearch4type1diabetes.blogspot.com
Mouse blog: http://t1dcuredinmice.blogspot.com/

9 comments:

Anonymous said...

Hi
I love your blog .. but this time I think you did not provide all the information available ...
In case you have missed it I strongly suggest watching this video with d-r Shapiro himself
http://www.sernova.com/i/video1/index-v1.html
Best Regards

Kristin said...

Great summary - thank you.

Anonymous said...

You should also consider reading this
http://www.sernova.com/s/RelatedArticles.asp?ReportID=516774&_Type=Related-Media-Articles&_Title=Ahead-Of-The-Herd-With-Sernova

Joshua Levy said...

For both Anonymous posters (April 6th and 17th): I had seen the video you suggest and read the posting you linked to before writing up the Sernova update. If you think I missed anything important, please be specific about what it is. I didn't seen anything new or uncovered in either of those sources.

Joshua Levy

Anonymous said...

Hi
its me again :)
Yes you are right .. you stated everything that is a known fact at the moment .. but what I miss is the optimistic view :) The animal study provided great results .. and Yes I know that in animals things are different .. but yet again .. the results are great ... and the fact that d-r Shapiro is behind all this makes me even more optimistic .. that's it
Regards

Joshua Levy said...

You don't need me for the optimistic view: you can read any company's press releases in a simple-minded and unquestioning way, and get the overly optimistic view. They are all going to cure type-1 in just a few years. :-)

Joshua

Anonymous said...

Love the blog! I think Sernova might be just the thing for the future of biotech companies. I love their approach. If you look, their publicly traded stocks today (4-23-2012)went up in value about 30% per share. I'm glad that there's a lot of companies who have tried to do this type of thing in the past, but Sernova has the money and research to back the human clinical trials. Now if I could just get into one of those... There's hope for the future.

Ula Mirjan said...
This comment has been removed by the author.
Wendy Rose said...

Hello!
I don't mean to leave a comment on an older post (okay, yes I do...but whatever...)

I'm sure you're aware of the DRI BioHub hype...just wanted to let you know that I'm anxious for your 2 cents, and also curious if I'm wrong by thinking this Sernova pouch and the BioHub seem very similar? I'm sure they're not, when you get down to the nitty gritty, but the two concepts sound very similar to me.

Anyway, I really appreciate and understand the way you share information, your logic, and your commitment to being as thorough as possible. THANKS!