Gene-edited pancreatic cells transplanted into a patient with type 1 diabetes(wired.com)
wired.com
Gene-edited pancreatic cells transplanted into a patient with type 1 diabetes
https://www.wired.com/story/no-more-injections-crispr-offers-new-hope-for-treating-diabetes/
71 comments
This is very encouraging, but will take a long time to get to any type of usable treatment because these cells are literally made to evade the immune system they run a whole bunch of other risks. Also cell therapies right now are one of the weakest markets in Biotechs due to the level of costs to develop. This is slightly different since it's Allogenic, but the market seems not very invested in cell therapy.
> This is very encouraging, but will take a long time to get to any type of usable treatment because these cells are literally made to evade the immune system they run a whole bunch of other risks. Also cell therapies right now are one of the weakest markets in Biotechs due to the level of costs to develop. This is slightly different since it's Allogenic, but the market seems not very invested in cell therapy.
If we're controlling the cells' genomes (which we are), we can add any sort of killswitch (see another comment https://news.ycombinator.com/item?id=45220068 ) that we would like, and this would function better than relying on host immune surveillance. The opposite could be done, making insulin release dependent on the presence of a harmless drug, e.g., insulin release can only happen if a designer steroid molecule is present in the blood.
There are already cell therapies that envisage permanent implantation of modified cells, so I am not sure why a long delay for 'any type of usable treatment' would occur. The structure of this need not be analogous to a stem cell transplant; you could imagine injecting new cells intramuscularly every few months.
The costs to develop this are incurred during development (unlike the autologous therapies that require extensive, expert-level analysis for each new patient). I'm not sure that we can compare the current levels of investment in autologous gene editing to this product.
If we're controlling the cells' genomes (which we are), we can add any sort of killswitch (see another comment https://news.ycombinator.com/item?id=45220068 ) that we would like, and this would function better than relying on host immune surveillance. The opposite could be done, making insulin release dependent on the presence of a harmless drug, e.g., insulin release can only happen if a designer steroid molecule is present in the blood.
There are already cell therapies that envisage permanent implantation of modified cells, so I am not sure why a long delay for 'any type of usable treatment' would occur. The structure of this need not be analogous to a stem cell transplant; you could imagine injecting new cells intramuscularly every few months.
The costs to develop this are incurred during development (unlike the autologous therapies that require extensive, expert-level analysis for each new patient). I'm not sure that we can compare the current levels of investment in autologous gene editing to this product.
Kill switch is a possibility, but once you start adding more than one item to a cell it doesn't always work out. What I mean is that the number of cells that successfully take both edits and continue to operate normally or survive the editing process drops considerably.
You are correct that current cell transplant therapies exist, but I don't believe any before have contained these immune escaping edits and I believe all of those treatments are cancer treatments which allow for a different level of risk. Diabetes is a very serious disease but a quality of life treatment does exist and having cells result in a potential cancer in patients would not be acceptable as an outcome.
You are correct that current cell transplant therapies exist, but I don't believe any before have contained these immune escaping edits and I believe all of those treatments are cancer treatments which allow for a different level of risk. Diabetes is a very serious disease but a quality of life treatment does exist and having cells result in a potential cancer in patients would not be acceptable as an outcome.
This is an area I work in professionally so I keep up with the technical side of things.
> once you start adding more than one item to a cell it doesn't always work out.
Very true, but the amounts of money at stake would justify the relatively inexpensive cost of hooking cells up to the already-available ER/TR-responsive gene elements.
> but I don't believe any before have contained these immune escaping edits
Hard to say, I'm not an expert on immune escape. It's an old idea, however, so I imagine it's been used in other pre-clinical or Phase 1 settings.
> I believe all of those treatments are cancer treatments which allow for a different level of risk
I imagine you're speaking about allogeneic treatment? Either way, this isn't true at all - here's a list of current treatments for diabetes alone:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12401705/#s4
> once you start adding more than one item to a cell it doesn't always work out.
Very true, but the amounts of money at stake would justify the relatively inexpensive cost of hooking cells up to the already-available ER/TR-responsive gene elements.
> but I don't believe any before have contained these immune escaping edits
Hard to say, I'm not an expert on immune escape. It's an old idea, however, so I imagine it's been used in other pre-clinical or Phase 1 settings.
> I believe all of those treatments are cancer treatments which allow for a different level of risk
I imagine you're speaking about allogeneic treatment? Either way, this isn't true at all - here's a list of current treatments for diabetes alone:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12401705/#s4
I also work in this field and while I largely agree with you, cell therapy is one of the hardest hit fields right now financially and investing in big shots to do something like dual edited islet cells is probably not going to happen. Maybe in the distant future, but right now I don't see someone going for that seriously in a clinical setting.
"you could imagine injecting new cells intramuscularly every few months"
So, a subscription... ouch.
I get the medical advantages, but it still sounds as easily abusable economically.
So, a subscription... ouch.
I get the medical advantages, but it still sounds as easily abusable economically.
This is great news. Any type of pancreatic function restoration is also potentially good for Type 1.5 (which constitute a sizable chunk of misdiagnosed T2Ds) where the body attacks more slowly (over the course of years) instead of acutely like traditional T1D and so doctors assume it's insulin resistance instead of pancreatic function decline since they both present with the same symptom - hyperglycemia.
It would be nice if fasting insulin and other markers were tested more regularly beyond fasted glucose and a1c, since those can vary for other reasons. Not to mention catching those developing insulin resistance potentially years ahead.
A1c is simple, easy, reliable and readily available. You might not spot the early signs with T2 due to natural variations but it's definitely a good test for T1. Don't rule it out completely.
Agreed mostly. It's a great test. There is a slight complication because it depends on the amount of glycation "damage" that the red blood cells receive over their lifetime of a few months, so if a patient has a condition that means their red blood cells have a non-standard lifetime (for example if they have sickle cell disease) then the HbA1c measurement becomes non-standard as well.
The other thing a HbA1c measurement isn't so good for is detecting blood sugar spikes (which are really bad for you) and distinguishing that from a constant slightly higher blood sugar level (which isn't such a big deal). For instance, there's a reasonably rare condition called GCK MODY which causes the body to have a slightly higher blood glucose "set level", which shows up very clearly on a HbA1c measurement, tends to get clinicians to panic, and gets patients put on drugs or insulin which they do not need and in fact is harmful to them. My lab does many genetic tests for this condition (among others) and a fairly common message back to the clinician is to take them off all treatment.
The other thing a HbA1c measurement isn't so good for is detecting blood sugar spikes (which are really bad for you) and distinguishing that from a constant slightly higher blood sugar level (which isn't such a big deal). For instance, there's a reasonably rare condition called GCK MODY which causes the body to have a slightly higher blood glucose "set level", which shows up very clearly on a HbA1c measurement, tends to get clinicians to panic, and gets patients put on drugs or insulin which they do not need and in fact is harmful to them. My lab does many genetic tests for this condition (among others) and a fairly common message back to the clinician is to take them off all treatment.
Similarly, in carnivore circles... doctors will try to put you on metformin or other medications when you hit 5.7 even though you do emphatically not have elevated glucose levels. The working hypothesis is that the cells are living longer so seeing slightly higher total glycation.
Of course this is similar to ongoing lack of understanding in terms of cholesterol health. I've learned to pretty much only care about my TG/HDL ratio.
Aside: my mostly carnivore/keto diet is pretty much the only course of diabetes treatment that has worked well for me over time... Trulicity/Ozempic ruined my life, and I've responded badly to very badly to almost every medication I've ever been given.
Of course this is similar to ongoing lack of understanding in terms of cholesterol health. I've learned to pretty much only care about my TG/HDL ratio.
Aside: my mostly carnivore/keto diet is pretty much the only course of diabetes treatment that has worked well for me over time... Trulicity/Ozempic ruined my life, and I've responded badly to very badly to almost every medication I've ever been given.
There are also loads of tests for antibodies now; some are even (gasp) free for qualifying people. More here: https://www.breakthrought1d.org/early-detection/#screening-o...
BTW Covid harms pancreatic cells that produce insulin via autoimmune mechanisms.
That's really exciting news. There's a couple non-immunosuppressed solutions being tested, hopefully one pans out.
Yep, I think vertex is one of the companies trying to tackle an encapsulated set of insulin producing cells.
Neat stuff!
Neat stuff!
Here's a list of all the biosimilar products in this space:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12401705/#s4
https://pmc.ncbi.nlm.nih.gov/articles/PMC12401705/#s4
This seems like it’s on the right track. Finally something that doesn’t require immunosuppressants.
It was in people and not mice too. So many of these headlines are in cell cultures or mice.
N=1 study should not have made it into headlines.
> Although the research marks a milestone in the search for treatments of type 1 diabetes, it’s important to note that the study involved one one participant, who received a low dose of cells for a short period—not enough for the patient to no longer need to control their blood sugar with injected insulin. An editorial by the journal Nature also says that some independent research groups have failed in their efforts to confirm that Sana’s method provides edited cells with the ability to evade the immune system.
> Although the research marks a milestone in the search for treatments of type 1 diabetes, it’s important to note that the study involved one one participant, who received a low dose of cells for a short period—not enough for the patient to no longer need to control their blood sugar with injected insulin. An editorial by the journal Nature also says that some independent research groups have failed in their efforts to confirm that Sana’s method provides edited cells with the ability to evade the immune system.
Despite that, glad to see it in a human subject.
I’ve had T1D for more than 30 years and have seen every headline under the sun with a “cure” always sometime in the next 5 years, so my expectations are properly tempered.
Still excited by it but a long way from clinics handing this out as a solution (if it’s viable).
I’ve had T1D for more than 30 years and have seen every headline under the sun with a “cure” always sometime in the next 5 years, so my expectations are properly tempered.
Still excited by it but a long way from clinics handing this out as a solution (if it’s viable).
5 years is modern for a long time. Used to be in the next decades. I've had it for about the same time and about 10 years ago I stopped following all research since it never goes anywhere. I'll wait till they start doing late stage trails to be even interested to read the full report.
The thing is that with such a sample, we don't really know
1. If the effect is real. i.e. had the patient not been given the injection, would his/her condition improve spontaneously.
2. Assuming the effect is real, what are the circumstances that make the treatment work for this person.
Not to be overly dismissive of the good work but it is too early to be optimistic about this given the above and the fact that the results were not replicated out of Sana suggest that there is a lot that we need to work out before this becomes a viable treatment for the masses.
The harms of hyping this up is that readers will get their hopes up and then be disappointed when things don't pan out as do most scientific endeavours. Overtime, readers will learn to distrust anything that is being reported because 90% of which do not translate to real world impact. It is hard to get the nuance that "science takes many many failures and iterations" to the public and the more likely outcome of such reporting is general distrust of science when things don't go the way that is hoped for.
1. If the effect is real. i.e. had the patient not been given the injection, would his/her condition improve spontaneously.
2. Assuming the effect is real, what are the circumstances that make the treatment work for this person.
Not to be overly dismissive of the good work but it is too early to be optimistic about this given the above and the fact that the results were not replicated out of Sana suggest that there is a lot that we need to work out before this becomes a viable treatment for the masses.
The harms of hyping this up is that readers will get their hopes up and then be disappointed when things don't pan out as do most scientific endeavours. Overtime, readers will learn to distrust anything that is being reported because 90% of which do not translate to real world impact. It is hard to get the nuance that "science takes many many failures and iterations" to the public and the more likely outcome of such reporting is general distrust of science when things don't go the way that is hoped for.
Type 1 diabetes does not spontaneously resolve
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This study's pretty wild -- but this approach has a major downside that they only mentioned in passing in the actual report in the New England Journal of Medicine (paywalled, unfortunately).
To gene-edit these cells, they had to use a lentivirus vector -- a (limited form of a) class of viruses that notably includes HIV. These viral vectors work by splicing themselves into random places in the host cell's DNA. Which is fine, except that there's a non-zero chance that in the process, the virus will initiate a cancer.
When you combine that with a cell deliberately engineered to hide from the immune system, you have the ticket to a very bad time.
To gene-edit these cells, they had to use a lentivirus vector -- a (limited form of a) class of viruses that notably includes HIV. These viral vectors work by splicing themselves into random places in the host cell's DNA. Which is fine, except that there's a non-zero chance that in the process, the virus will initiate a cancer.
When you combine that with a cell deliberately engineered to hide from the immune system, you have the ticket to a very bad time.
One would probably engineer these cells with a killswitch, such as doxycycline induced Caspase9 https://pmc.ncbi.nlm.nih.gov/articles/PMC1895037/.
The transgene engineering is totally possible without a viral vector. We engineer cells all the time with recombinase based editing methods for targeted safe harbor insertion of transgenes https://www.nature.com/articles/s41551-024-01227-1. This stuff just permeates through the community slowly.
The transgene engineering is totally possible without a viral vector. We engineer cells all the time with recombinase based editing methods for targeted safe harbor insertion of transgenes https://www.nature.com/articles/s41551-024-01227-1. This stuff just permeates through the community slowly.
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Because it has been commented over and over "oh, type 2 is because you are overweight"...
> We tend to think of type 2 diabetes as a disease that afflicts people who are overweight. But it can also appear in people with perfectly healthy weights—and be more deadly in them. A study published today in the Journal of the American Medical Association indicates that normal-weight people diagnosed with type 2 diabetes have double the risk of dying from heart disease and other causes than overweight people with diabetes.
- https://www.health.harvard.edu/blog/diabetes-can-strike-hard...
(Yes, I know this post is about Type 1... but _all_ of the talk in it when I posted this was about Type 2; and basically blaming the people with it for their condition)
> We tend to think of type 2 diabetes as a disease that afflicts people who are overweight. But it can also appear in people with perfectly healthy weights—and be more deadly in them. A study published today in the Journal of the American Medical Association indicates that normal-weight people diagnosed with type 2 diabetes have double the risk of dying from heart disease and other causes than overweight people with diabetes.
- https://www.health.harvard.edu/blog/diabetes-can-strike-hard...
(Yes, I know this post is about Type 1... but _all_ of the talk in it when I posted this was about Type 2; and basically blaming the people with it for their condition)
But being overweight is a huge risk factor for developing it and absolutely can contribute to it. I don't how it being more deadly in skinny people detracts from that or is relevant at all.
Because people (who don't know what they're talking about) respond with statements like "you can cure Diabetes Type 2 with diet and exercise", and
- That's false. For _most_ people, you can prevent the symptoms of it with those, but not all. Nor does it _cure_ it, it prevents it from presenting symptoms. The same way that avoiding a food you are allergic to doesn't cure the allergy, it just prevents it from impacting you
- It's insulting to a lot of people that _are_ eating and exercising well, but still battling with Diabetes Type 2
It's wrong and it's insulting.
- That's false. For _most_ people, you can prevent the symptoms of it with those, but not all. Nor does it _cure_ it, it prevents it from presenting symptoms. The same way that avoiding a food you are allergic to doesn't cure the allergy, it just prevents it from impacting you
- It's insulting to a lot of people that _are_ eating and exercising well, but still battling with Diabetes Type 2
It's wrong and it's insulting.
Even if you are overweight... it's NOT easy to lose weight.. especially if you've lost a significant amount of weight in your life. You may well have a really dysfunctional metabolism, and most advice is just bad for this case. Many people actually have to eat more of a reduced menu in order to lose weight.
I'm a pretty big fan of carnivore for this, which has its own detractors, and countering half a century of misinformation of meat and fat isn't the easiest thing in the world. And even then, you may still need some level of supplemental insulin for a long while.
That isn't to say I support general gluttony and laziness... but it isn't that easy, and its even harder when people just assume you aren't even trying or have negativity towards you in general. You try to work out and you get dirty looks and stares... you are eating out (healthy options) but again, dirty looks and stares... it doesn't help.
I'm a pretty big fan of carnivore for this, which has its own detractors, and countering half a century of misinformation of meat and fat isn't the easiest thing in the world. And even then, you may still need some level of supplemental insulin for a long while.
That isn't to say I support general gluttony and laziness... but it isn't that easy, and its even harder when people just assume you aren't even trying or have negativity towards you in general. You try to work out and you get dirty looks and stares... you are eating out (healthy options) but again, dirty looks and stares... it doesn't help.
it's one factor but weight and diet isn't the only component
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type 2 is more closely associated with genetics than type 1
https://diabetes.org/about-diabetes/genetics-diabetes
https://diabetes.org/about-diabetes/genetics-diabetes
That's not true. From the article, type 2 is more familial than type 1, but not all of that association is genetic.
As a more concrete demonstration, the type 1 genetic risk score (GRS) has good predictability of the risk of someone getting type 1 diabetes. We have linked certain genetic variants to increased or decreased risk of getting type 1 diabetes (and it's mostly in the HLA complex on chromosome 6 that significantly influences the immune system). The AUC (area under curve) of the score's ROC curve is 0.87, which is good. We use the type 1 GRS for patients incoming with type 1-like symptoms to separate out those likely to have rare genetic conditions instead, alongside antibody testing, and it works very well.
The type 2 GRS is very weak in comparison. We haven't found much link between genetics and type 2 risk that we can use to predict the risk. The AUC of the type 2 GRS is only 0.63 in the very best studies, which is a poor predictor.
Having said that, type 2 risk varies quite considerably with race, with South Asians being more susceptible to type 2 diabetes than much of the rest of the world.
Note, an AUC of 0.5 indicates no predictive value whatsoever, and an AUC of 1.0 indicates perfect prediction.
As a more concrete demonstration, the type 1 genetic risk score (GRS) has good predictability of the risk of someone getting type 1 diabetes. We have linked certain genetic variants to increased or decreased risk of getting type 1 diabetes (and it's mostly in the HLA complex on chromosome 6 that significantly influences the immune system). The AUC (area under curve) of the score's ROC curve is 0.87, which is good. We use the type 1 GRS for patients incoming with type 1-like symptoms to separate out those likely to have rare genetic conditions instead, alongside antibody testing, and it works very well.
The type 2 GRS is very weak in comparison. We haven't found much link between genetics and type 2 risk that we can use to predict the risk. The AUC of the type 2 GRS is only 0.63 in the very best studies, which is a poor predictor.
Having said that, type 2 risk varies quite considerably with race, with South Asians being more susceptible to type 2 diabetes than much of the rest of the world.
Note, an AUC of 0.5 indicates no predictive value whatsoever, and an AUC of 1.0 indicates perfect prediction.
Type 2, they need to solve type 2.
If GLP-1 Drugs Are Good for Everything, Should We All Be on Them? - https://news.ycombinator.com/item?id=44830685 - August 2025
There have been a lot of advancements on this front too. One promising technique is duodenum resurfacing (DMR). This helps reset some of the insulin sensitivity issues. The one problem we have is that this is a one time low risk procedure compared to selling insulin or GLP-1. Like all of our problems in healthcare, we have a major misalignment in incentives.
isn't that what GLP1s are for (before you get full blown type 2)
Yes, but even lifestyle changes (like a diet low in glycemic load and building muscle) can help reduce many of the harmful effects of type 2 diabetes, even sending it into remission for some people in early stages.
Type 1 is a different story. It’s the lack of natural insulin production (due to a damaged pancreas, autoimmune or other causes), basically the opposite problem to type 2, and no amount of lifestyle changes will replace of need of insulin doses.
Type 1 is a different story. It’s the lack of natural insulin production (due to a damaged pancreas, autoimmune or other causes), basically the opposite problem to type 2, and no amount of lifestyle changes will replace of need of insulin doses.
I just want to make clear what the other commenter said: type 2 is completely reversible in its early stages. Lose weight, eat a more healthy diet, and you should see your body return to normal.
Unfortunately, there's a serious time limit on this news, as the disease does permanently damage your cells, but in a way that's not terrible. It's probably easier to be shocked by a diagnosis into a lifestyle change than to find out now and undo 30 years of living with daily insulin injections anyways.
Unfortunately, there's a serious time limit on this news, as the disease does permanently damage your cells, but in a way that's not terrible. It's probably easier to be shocked by a diagnosis into a lifestyle change than to find out now and undo 30 years of living with daily insulin injections anyways.
If you treat sugar as an addiction you can solve it yourself.
moi2388(2)
Just sent this to my son, seems legitimately promising