Pluripotent stem cell replacement to treat type 1 diabetes

[Loui]

Researches are studying hard to replace stem cells in type 1 diabetes. Because, pluripotent stem cells can produce functional β-like cells. But I have a question. Non-functional β cells in type 1 diabetes are the result of immune response. So, your blood consists of memory T and B lymphocytes which target your own pancreatic cells as enemy. So, even if you replace your non-functional cells, they will maintain targeting and harm your own cells. So why are the scientists trying to solve a problem in that way? If they replaced the harmed cells with functional cells, would it be a persistent treatment? Isn't it logical? 

[Dagl1]

1 hour ago, Loui said:

Researches are studying hard to replace stem cells in type 1 diabetes. Because, pluripotent stem cells can produce functional β-like cells. But I have a question. Non-functional β cells in type 1 diabetes are the result of immune response. So, your blood consists of memory T and B lymphocytes which target your own pancreatic cells as enemy. So, even if you replace your non-functional cells, they will maintain targeting and harm your own cells. So why are the scientists trying to solve a problem in that way? If they replaced the harmed cells with functional cells, would it be a persistent treatment? Isn't it logical? 

Can you provide evidence that T1 diabetes is the result of autoimmune activity, as far as I know (but I am not very up to date in this field) we currently have no clear causal relationship, only several risk factors and some hypotheses?
If it is the case, one possibility would be to use immunosuppresive drugs in combination with this treatment, or find out if it is possible to use pluripotent stem cells of another person (potentially modified to not alert the immune system of foreign tissue). 

Dagl

[iNow]

15 minutes ago, Dagl1 said:

Can you provide evidence that T1 diabetes is the result of autoimmune activity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687512/

Quote

the notion that T1D is caused by an autoimmune T cell response against the insulin‐producing beta cells is supported by genetic evidence, histology, intervention trials and in‐vitro analysis of T cells. There are many gaps in our knowledge, including the nature of the initial event that triggers the autoimmune response that leads to T1D. Nonetheless, discarding the autoimmune model of T1D is, in our view, not supported by the evidence. Importantly, an alternative model of the aetiology of T1D must account for the observations that have already been confirmed by multiple studies.

<...>

While acknowledging the many challenges associated with studying T1D in humans we argue that the evidence, accumulated over decades, supports the view that T1D in humans, like the NOD mouse, is caused by autoimmune T cell responses against the pancreatic beta cells. 

 

[Loui]

 

21 minutes ago, Dagl1 said:

Can you provide evidence that T1 diabetes is the result of autoimmune activity, as far as I know (but I am not very up to date in this field) we currently have no clear causal relationship, only several risk factors and some hypotheses?
If it is the case, one possibility would be to use immunosuppresive drugs in combination with this treatment, or find out if it is possible to use pluripotent stem cells of another person (potentially modified to not alert the immune system of foreign tissue). 

Dagl

Here, it says an autoimmune disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219937/

I wonder why scientists are trying to solve this problem by not targeting the roots of disease. We have already a solution like insulin injection, and it is a very cheap way. Our immune system can harm the new pancreatic  β celss again in 1-2 year maybe and the same processes will be repeated. So, this is not a logical approach.

Edited May 10, 2019 by Loui

[Dagl1]

1 minute ago, iNow said:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687512/

 

Interesting, but shouldn't that mean that suppressing the immune system would alleviate T1 diabetes (or well, I suppose we can't assume that the damaged cells will repair themselves and I don't know if these cells are actively being renewed)? 

I suppose immune suppression does have some beneficial effects, but I also realize that the cons may not outweigh the gain. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405831/ 

Dagl

5 minutes ago, Loui said:

 

Here, it says an autoimmune disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219937/

I wonder why scientists are trying to solve this problem by not targeting the roots of disease. We have already a solution like insulin injection, and it is a very cheap way. Our immune system can harm the new pancreatic  β celss again in 1-2 year maybe and the same processes will be repeated. So, this is not a logical approach.

I think the root of the problem (B/T cells) are a bit more difficult to target/modify, and as the trigger of their autoimmune activity doesn't seem to be known, we cannot stop it from happening again if we could fix it. As I mentioned in my first reply, there is of course the possibility of modifying the beta cells in such a way that the immune system may not target them or combine it with general immunosuppressive medication.

-Dagl

[iNow]

9 minutes ago, Loui said:

We have already a solution like insulin injection

That's a treatment, not a solution

5 minutes ago, Dagl1 said:

shouldn't that mean that suppressing the immune system would alleviate T1 diabetes (or well, I suppose we can't assume that the damaged cells will repair themselves

You've answered your own question. The damage is done already. Suppressing the immune system will just cause other new problems for health.

[Loui]

1 minute ago, iNow said:

That's a treatment, not a solution

Yes, you are right I meant it was a treatment. 

[iNow]

Just now, Loui said:

Yes, you are right I meant it was a treatment. 

The basic idea here is this: Should we just keep applying band-aids, or should we instead try to stop the bleeding?

[Loui]

4 minutes ago, iNow said:

The basic idea here is this: Should we just keep applying band-aids, or should we instead try to stop the bleeding?

Yes, we should stop bleeding but the replacement approach does not stop bleeding. Some studies are just aiming a second temporary treatment with huge budgets. Why is that happened? Because of that money? Maybe some another companies want to own this monopoly and try to find new second way to make all of the money here. Because it is a temporary way to treat the disease. After 1-2 years, patient should be treated again and again. So companies can make money continuously.

Edited May 10, 2019 by Loui

[iNow]

I only know lots of people are looking for ways to eliminate diseases like this at the source. There is a lot of activity around genetic testing or modification, often using tech like CRISPR.

Interestingly, since you mention money, that tends to lean AGAINST solving T1D. Why is that? Diabetics serve as a consistent and reliable revenue stream for pharma companies since they need to buy insulin and glucose test strips every month. Implementing a cure means Eli Lilly, Novo Nordisk, and Sanofi will suffer financially, thus all have a vested interest in maintaining the status quo.

Focusing on a cure is done for humanitarian reasons because it's the right thing to do, or maybe because someone wants to win a nobel prize and be remembered. I wouldn't speculate that most folks are "in it for the money," though. 

[PhilGeis]

There are effectively three companies producing insulin for the world.  Rather than holier-than-thou "big pharma" bashing, consider for one Lilly's current reported diabetes research https://www.lilly.com/partners/scientific-areas-of-interest  as well as NIH billion+  diabetes research program https://www.niddk.nih.gov/about-niddk/budget-legislative-information/diabetes-research-improving-lives-path-cure-2015.

 

[iNow]

I’m not bashing big pharma. I’m bashing price gouging on products people will die without, even when the formulation and manufacturing cost is completely unchanged for decades.

I’m also making an entirely valid business comment. Nothing to do with morality or bashing.

A cure is not in the financial interest of these companies given the impact on their current predictable revenue streams. That’s so obvious it shouldn’t even need saying. 

Edited May 29, 2019 by iNow

[PhilGeis]

The original post focused  therapies and prevention not on price.  Since you've focused on price, mind sharing the claimed validation?   Shouldn't be hard since so obvious - or is it a bias?. and please understand "big pharma" is more than the three insulin suppliers.  If others could obtain a share - or all of the diabetes business - they would.

I don;t know the price structure or understand why  costs have doubled just in this decade.   Lilly for one offers what appears to be a tangential  response that doesn't answer the question .  https://www.cnbc.com/2019/03/25/eli-lilly-discloses-pricing-data-for-its-popular-insulin-humalog.html

as you claim to know = what are the manufacturing and materials costs through the decades?    

Spoiler

 

 

Separately - do agree with iNow's comment were lifetime immunosuppressive therapy the risks of which are probably much greater than the current insulin therapy .

Edited May 29, 2019 by PhilGeis

[dimreepr]

3 minutes ago, PhilGeis said:

The original post focused  therapies and prevention not on price.  Since you've focused on price, mind sharing the claimed validation?   Shouldn't be hard since so obvious - or is it a bias?. 

I don;t know the price structure or understand why  costs have doubled just in this decade.   Lilly for one offers what appears to be a tangential  response that doesn't answer the question .  https://www.cnbc.com/2019/03/25/eli-lilly-discloses-pricing-data-for-its-popular-insulin-humalog.html

as you claim to know = what are the manufacturing and materials costs through the decades?    

  Reveal hidden contents

 

 

It's not about actual costs, it's about exclusivity; generic drugs cost almost nothing. 

 Big pharma just exploits death and the governments disinterest, much like the defence industry.   

[iNow]

46 minutes ago, PhilGeis said:

what are the manufacturing and materials costs through the decades?    

This article and the citations within offer clarity on your request:

* Gotham D, Barber MJ, Hill A. Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Global Health 2018;3 (link)

 

Here's a nice layman's review that may help depending on your existing knowledge of the topic: Insulin prices could be much lower and drug makers would still make healthy profits (link)

 

The two citations from that first study most closely related to this tangent are as follows:

* Luo J , Kesselheim AS. Evolution of insulin patents and market exclusivities in the USA. Lancet Diabetes Endocrinol 2015;3:835–7; (link)

* Kaplan WA , Beall RF. The global intellectual property ecosystem for insulin and its public health implications: an observational study. J Pharm Policy Pract 2017;10:3; (link)

 

I hope this helps. Now... Unless you're suggesting that manufacturing costs have increased 197% in 10 years in a pattern that matches the price gouging, then my original point stands and will remain valid no matter how niggling at the irrelevant margins you send my way in future replies.

[PhilGeis]

Oh sure, they are all evil.  Perhaps you shouldn't presume others would apply your morals.  Government disinterest?  With > billion in funding diabetes research-(that's just the NIH) and grant recipients eager for their own startup opportunities?  If there is gov "disinterest" its lies in pressuring appropriate costs and that is clearly an open question for this and many drug products.

Think you guys fail to understand how business thinks long term - developing technology has no exclusivity.    Let me help you understand how business sees technology.  Please consider the lesson taught in business schools as well as business training in all major companies. In 1975 Kodak developed digital photography, a technology they chose not to develop and market as it would cannibalize their existing film/camera business.  Kodak employed ~150,000 FTE’s globally at that time.  in the 90's the technology was marketed by other folks–  Kodak could not catch up and lost ~ everything, declared bankruptcy in 2012.  Their plan - sell the patents they still possessed and get into the copier business with remaining  ~2000 FTE’s.   https://www.nytimes.com/2015/03/22/business/at-kodak-clinging-to-a-future-beyond-film.html

The lesson  – that Lilly et al fully understand – technology will bring advances that can obsolete your core business.  You’ll not know this unless you pursue its development and, if it is discovered, you’re screwed if you don’t own it.

I hope the above helps.  I know it easy to throw some references on a post. - but i think there was reference to validity and specifics.  .  Can you take me through the claimed validation and again  - can you please review materials and manufacturing costs.  I'm suggesting nothing re. the latter - it was your affirmative statement about which I inquired "...formulation and manufacturing cost is completely unchanged for decades."

 

Edited May 29, 2019 by PhilGeis

[dimreepr]

1 minute ago, PhilGeis said:

Oh sure, they are all evil.  Perhaps you shouldn't presume others would apply your morals. 

They're not evil...

3 minutes ago, PhilGeis said:

Government disinterest? 

They just care about the voters ability to vote.

 

[iNow]

8 minutes ago, PhilGeis said:

Oh sure, they are all evil. 

Nobody here, as best I can tell, is arguing this. In the interest of clarity... Do you have any other strawmen you plan to erect and attack?

8 minutes ago, PhilGeis said:

Think you guys fail to understand how business thinks long term

It's interesting that you would make this assertion given how the following points you make align precisely with what I said... the cure is not in their financial interests. Keeping a revenue stream from an ever growing population of patients who need recurring treatment that has stable and decreasing costs of manufacture is.

Edited May 29, 2019 by iNow

[PhilGeis]

No - neither argument /attack  here or before. So you haven't read the citations sufficiently to summarize the "validity' claimed and do not have support for "...formulation and manufacturing cost is completely unchanged for decades."

Please recall these were your statements.  

[iNow]

yup

[dimreepr]

2 minutes ago, PhilGeis said:

No - neither argument /attack  here or before. So you haven't read the citations sufficiently to summarize the "validity' claimed and do not have support for "...formulation and manufacturing cost is completely unchanged for decades."

Please recall these were your statements.  

Rito

[iNow]

In hopes of moving this conversation forward, I should’ve have said manufacture costs are completely unchanged. Better would have been “don’t scale with the enormous increases in costs we’ve witnessed.” 

[dimreepr]

2 minutes ago, iNow said:

In hopes of moving this conversation forward, I should’ve have said manufacture costs are completely unchanged. Better would have been “don’t scale with the enormous increases in costs we’ve witnessed.” 

Business has to consider cost as a 1 for 1, but sometimes a government gets the luxury to put a man on the moon.

[PhilGeis]

I understand the perception re manufacturing but that's still subjective on our part.  I'm sure capital investment, research, compliance and controls have increased nominal costs but they may well have been limited by efficiencies, and big increases in so few years is tough to understand. 

Lilly et al. should answer the question and to dimreep's point, gov should pressure for that answer.  But 1 for 1?  man on the moon?  don't understand the meaning of the former and the latter return has just been funded for 1.6 billion - certainly not at the cost of NIH budget.

Strawman?  I'll offer what i see as  relevance of the Kodak lesson.  It was intended to address  the comment that money is against solving the issues with diabetes.  With > billion in research for diabetes, if there is a "cure"  or "prevention" to be discovered - Lilly and the other 2 would be foolish if they didn;t both carefully follow current research as well as maintain their own effort.    A single pivotal publication could immediately hit their stock price - a temporary inconvenience - if/until with success the happy researcher formed his/her own startup.  No impact on insulin profits yet - just as Kodak saw no impact on theirs until ~ turn of the century.  Presuming additional success the startup technology goes to the highest bidder or is knocked off by somebody else.    Again presuming success - it is only a matter of time. 

[iNow]

3 hours ago, iNow said:

In hopes of moving this conversation forward, I *should’ve have said* manufacture costs are completely unchanged. Better would have been “don’t scale with the enormous increases in costs we’ve witnessed.” 

*shouldn't have said...