A Travesty !? - Promising Sjogren's Vaccine Shelved - Lack of Funding ?!

[nisha]

kindandcaring -

I gather that nobody at the SSF ever managed to talk with the researchers.  Phone calls were not returned and correspondence was ignored.  As you say, too bad we are not in Toronto so we could march in and bang on their desk.

[kindandcaring]

Yeah...you are right nisha... !!

Now we Know that a comm's issue Does exist !

Anyone in Toronto ? interested in finding out for us ?

I live in Australia..its out of my budget zone just to pop over..it would be easier for someone in Toronto region for sure..pretty please anyone up for it 

Until we know what the go is with the Researchers we will be forever wondering..

There are a lot of us..Sjogrens Sufferers...we need to show our will to want to get better and communicate with these Researcher guys ..that we want and need their help..if they have a Vaccine and believe it could work then let them tell us what has stopped any further progress..and let them tell us what would it take to start it rolling again...

You could argue that an explanation does not have to be forthcoming...actually I think it is absolutely..
To ignore offers of funding after being we had been told they have no funding..means they absolutely need to clarify for all of us what are the reasons..for the halt on the Vaccines progress and its current status and it's future..!

If there had been a Vaccine for say HIV and it was published around the world as THE BREAKTHROUGH for that disease..then the question ..would it be allowed to be forgotten  by the media the public..governments !?
I think the answer is no..questions would be asked and answers expected as to why a HIV Vaccine's progress had stopped ..


Anyone got ideas how to get an outcome ? keeping in mind their seems to be a complete communication breakdown at the moment...!

[Linda196]

I have a friend on the Canadian Association of Research Ethics Boards, and she is going to look into the whole thing for me... I'll let you all know what she finds out.

[nisha]

Linda -

Can hardly wait to hear what she finds out.

nisha

[irish]

I am still ruminating over Nisha remark----If we don't know what is specifically causing Sjogrens how can we produce a vaccine. Good question. Irish

[kindandcaring]

I have a friend on the Canadian Association of Research Ethics Boards, and she is going to look into the whole thing for me... I'll let you all know what she finds out.

Sounds like a good move Linda..thanks heaps for your efforts with this !

[kindandcaring]

I am still ruminating over Nisha remark----If we don't know what is specifically causing Sjogrens how can we produce a vaccine. Good question. Irish

Hi Irish
Yeah it is a good question. I had a go in an earlier post to try and explain ..I could be wrong though Im speaking in general terms...to help you and others Ive posted a link to the Patent the researchers have filed..it does explain things technically ...one can however figure it out by reading the overview/summary..and repeatedly skimming.

http://www.pat2pdf.org/patents/pat20080058271.pdf


ICA69 (Islet Cell Autoantigen 69)

ICA69 is the target for their  candidate 'Peptide' Vaccine to prevent Sjogrens...the Vaccine makes the recipient ICA69 deficient..in the mice becoming deficient of ICA69 provoked the positive response ...a response even in mice who had fully develop Sjogren's.


If anyone can explain it better please do share..Im trying to explain it more simply and (almost) in a one liner as best I can..but I might have missed something in the translation...its certainly can be improved upon 

I will be giving a copy of the patent to my Immunologist in a few weeks for his perusal (and hopefully some comment)

[jjj3]

kindandcaring - Thank you for keeping this post alive!  Hopefully we'll get some info. soon.

Linda - what a great contact to have!  I hope your friend has better luck contacting these guys than SSF has had.  I'm assuming she will, given that she is on the Research Ethics Board.  Thank you!

Cathy

[nisha]

kindandcaring -

Thanks for the link to the Patent.

I guess the part I don't understand is that a vaccine is generally given to prevent a disease, yet this says  that  "..in the mice becoming deficient of ICA69 provoked the positive response ...a response even in mice who had fully developed Sjögren's".  

If the mice already have sjs, then how can it be a vaccine instead of a medicine to either alleviate symptoms or cure the disease?

nisha

[Linda196]

A vaccine is a biological preparation which is used to establish or improve immunity or resistance to a particular disease. The basic difference between a drug and a vaccine is the biological source, and even that doesn't always stand up, because more and more drugs are being developed from recombinant DNA.

Vaccines can be prophylactic (e.g. to prevent or lessen the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated).

[nisha]

Every definition I find states that a vaccine is used to prevent a disease, so I am still confused how it can work in mice who already have sjs.  Sorry if I am being dense.

nisha

[Linda196]

Nisha, this is the most comprehensive definition of vaccine that I could find:
http://www.online-medical-dictionary.org/Vaccines.asp?q=Vaccines

[Shawn]

Hello all,

I think that I can explain the ICA69 finding a little better [I wrote it after all  ]. Here is a long summary in lay terms.

First, ICA69 is a protein made in several tissues including the pancreas, nervous, salivary and lacrimal glands. The function of the protein is unknown. However, in certain autoimmune diseases, the bodies immune system mounts an abnormal immune response to ICA69. The response is considered abnormal because ICA69 is a self-protein as opposed to a foreign protein (like from a virus). This immune response can be measured by measuring antibodies or T cell responsiveness.

Before 2002, only Type 1 diabetes patients were known to have immunity to ICA69. Thus, when I was working in Dr. Dosch's lab as a PhD student at the time we wanted to see how important ICA69 was for the diabetes disease process. One way to do this is to take a mouse that gets diabetes and knock out that protein and then check to see is the knock out mouse still gets diabetes. We did this with ICA69 in NOD mice (these mice develop spontaneous diabetes, thyroiditis, and Sjogren's..though only the diabetes aspect of this mouse is extensively studied). The ICA69 KO mouse still got diabetes normally, meaning that ICA69 was not critical in that disease. However, to be complete we checked for Sjogrens as well, and surprisingly the mice developed markedly less disease. THat was how the ICA69 Sjogren's connection was founded.

Once we knew that ICA69 was important in Sjogren's syndrome in NOD mice, we wanted to see if dampening the immune response to the protein would reduce disease. This is called antigen based immunotherapy or immune modifying therapy and you are right "vaccine" is not the proper word. There are several ways to inject a protein into a mouse to elicit a dampening as opposed to an activating immune response. This was done in NOD mice that had full Sjogren's syndrome and the therapy significantly improved disease.

However, antigen based immunotherapy protocols work well in mice, but the protocols have not been standardized well in humans. For example, an immunotherapy trial was done for MS, but the trial was stopped because the patients got worse disease. A trial was done for T1 diabetes and showed no effect. That being said, there is new, promising data showing antigen based immunotherapy may work in humans if the patients previously showed strong response to the protein being used in the therapy. For example, in a newer T1 diabetes trial, patient's who had previous strong immune responses to insulin showed significant improvement when they received oral therapy insulin. But as you can see, this type of therapy is still being worked out in humans and it is being actively pursued by many labs.

We next tested to see if human SS patients also mounted abnormal immune responses to ICA69, and about 3/4 did. A slightly larger study using a different test (done by US and Australian researchers) found about 1/3 of Sjogren's patients targeted this protein. So... Will ICA69 immuotherapy work in humans? If the proper sub group of patients are selected (ie ones who respond to ICA69) then there is a chance that it could work, but, only if the immunotherapy protocol is first better understood for human use.

I left the lab in 2003 and went to medical school, but I came back several times to check on the progress (I finished medicine and am currently doing some research on type 2 diabetes before I start residency in July). Dr. Dosch told me that he wrote several grants on the role of ICA69 in Sjogrens...more specifically, to expand our initial patient numbers, to learn better of its diagnostic values, and to try begin a small trial to see if there is benefit for humans. However, for reasons that I do not know, every grant was turned down (but trials are very expensive, and lack of funding likely had a lot to do with it).

Hope this helped clarify some things,

Dr. Shawn Winer  MD, PhD

[kindandcaring]

Welcome Shawn 

Thankyou for popping in and sharing knowledge...it is I can assure you Most Appreciated..!

I never thought when I started the thread and mentioned the patent that yourself who wrote it would end up helping us explain it...it is Fantastic to hear you speak..thankyou !


On behalf of Everyone Also a huge thanks for all your work which we are talking about here. !!!!


Until you explained it I had been a little confused as to ICA69...now reading your explanation I can see that it is a protein produced by our bodies organs (pancreas salivary gland etc.) however it has no known function and has been seen to have become a target for our immune response..when one has certain Autoimmune Diseases...like Sjogrens.

Thanks also for the further explanation regarding how many Sjogrens people could have quantities of Autoantibodies against this protein....those that a proposed Vaccine could more likely help....even if we use 30% as the number of people it could treat (using the lower UK Australia Study numbers) .it could still equate to large numbers of people being helped...


Sounds in my humble viewpoint it is worth funding further...and hearing you explain that Dr Dosch tried several times to get funding....he must think it worthy as well.

So we are looking at a Big funding question..or why is it so (not being given funds)..!?
The other issue of course is we have some possible funds that could come through SSF but some kind of problem is stopping that message getting through....not sure still..however Linda might well find out for us through her contact.

Lets hope your work gets a chance to get to a clinical setting..I know we would all like to see it come good...realising at the same time that a lot has to occur for this to be successful and to get to that stage ..and that it might not prove successful... yet from the journey we could learn more from whatever the outcome.
Benefiting us all.

Yet we will never know unless we can get on that journey forward.
Thanks again for your contribution, on this subject and for your future studies.

Thanks Shawn...
btw curious to know how you came across us here !? 
All my very Best

[Linda196]

Hello Shawn, welcome to Sjogren's World and thank you very much for representing "the other side of the coin" so to speak. It is heartwarming to meet doctors like yourself and Dr Birnbaum (who also posts here in the nervous system threads) who are so involved in trying to improve life for SjS (and other autoimmune) sufferers.

These diseases must be both fascinating and frustrating to researchers, because each disease can vary so much in symptoms, presentation, pathology and response. As you mentioned, the ICA69 protein presents in varying portions of patients, and other facets differ as well, for example, some of our members have IgG deficit, while others have high counts; and even the specific markers are sometimes absent, or present in various combinations.

By the way, please feel free to mention to Dr Dosch that if and when he gets to the recruitment process, this forum has many eager and willing volunteers, if location can be overlooked!