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.
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.
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.
> 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.
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.
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.
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.
Readit News
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.
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.
So, a subscription... ouch.
I get the medical advantages, but it still sounds as easily abusable economically.
Neat stuff!
https://pmc.ncbi.nlm.nih.gov/articles/PMC12401705/#s4
> 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.
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).
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.
Deleted Comment
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.
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.