Stem cells for Diabetes: the danger of the word ‘cure’

There has been considerable discussion about the whether the media hyped the recent Harvard Diabetes stem cell paper (see top 10 takeaways of that paper) . I believe that this was greatly hyped.

This Harvard publication reported production of insulin-secreting cells from human embryonic stem cells (hESC). Newspapers around the world widely exaggerated the potential impact of this paper. They often used the word “cure”.

Stem Cell Diabetes Hype

Perhaps the worst offender was the Telegraph with their headline “Cure for Type 1 diabetes imminent after Harvard stem-cell breakthrough“. I’m not even going link to the article because that headline was so dumb. Many other papers also used “cure” in their article titles (see above). Harvard itself also issued a piece mentioning how this work brought a ‘cure” closer in the article subtitle.

I have tremendous respect for the Harvard researchers on this team and this paper is very important, but this situation got totally out of control.

The use of the word “cure” is something that should be carefully deliberated not just for Diabetes, but for any disease. We all want cures for various diseases, but a cure for anything is a high hurdle. It means that the disease is gone and not coming back. Ever.

I’m not a Diabetes expert, but my understanding is that in fact there may be no such thing as a cure for Diabetes. Even with a very effective treatment the patient would still have Diabetes. They would still need blood sugar monitoring. Their immune system would still be active against pancreatic cells. They may need insulin intermittently.

Perhaps one could argue that an “effective cure” might even be possible via stem cell-based technology in the form of life-long blood sugar control in the general absence of any other treatment. Again, that wonderful achievement seems at best a decade or more from where we are today. The more careful word to use is “treatment”. Still, an effective treatment would be incredibly exciting. It doesn’t have to be a total cure to be a game-changer.

What’s the harm in loosely using the word “cure” as something coming soon?

It falsely raises hopes and expectations of patients and others. Saying a “cure” is coming soon is hype. There is a fine line between maintaining appropriate energy and enthusiasm with the language that one uses and going too far. I believe in this case that things crossed that line to hype.

Top 10 Takeaways From Harvard Stem Cell Diabetes Paper

Harvard stem cells DiabetesThe idea of using stem cells to treat Type I Diabetes is very promising and could have huge practical impact. Real progress has been achieved toward this goal over the last decade. In perhaps another decade there might be a validated treatment.

A new stem cell paper has just come out in Cell from Harvard in this area. It reports making insulin-producing β cells from human embryonic stem cells (hESC) with the notion of some day using these cells to treat Diabetes. See graphical abstract at left from the paper. These β cells help Diabetic mice control their blood sugar. Very cool.

This is an important, exciting paper, but one that the media has for the most part totally hyped. For a balanced, well-researched newspaper article on this Harvard Diabetes research I recommend this piece by John Lauerman at Bloomberg. It’s also worth noting that the same Harvard team published another big Cell paper related to stem cells and Diabetes last year on a hormone they discovered called Betatrophin that stimulates cells to turn into β cells.

Here are my top 10 key take home messages for this new paper in the context of the larger field of stem cell-related Diabetes research.

  • There are many labs around the world working on research toward the goal of using stem cells as a basis to treat Diabetes. The Harvard work is notable, but should be discussed in this larger context.
  • For example, another entity, the privately held stem cell biotech ViaCyte, has an approved IND for an hESC-based Diabetes treatment and an approved device in the form of a capsule.
  • Harvard will also need some kind of capsulation technology/device, which it does not appear to have at present. Harvard team leader Doug Melton described such a needed device as a “tea bag” with the idea being that the cells inside sense blood sugar (which goes into the capsule from blood) and make insulin (which goes out into the blood), but no cells should be able to go in or out.
  • ViaCyte will start a clinical trial in as soon as a few months for their hESC-based Diabetes therapy.
  • Barring some major change in regulatory approach by the FDA, the Harvard stem cell Diabetes product probably won’t start to be tested in humans for at least about 4 years given the experiences of other groups using human embryonic stem cell-based products. It’s important to keep expectations realistic.
  • Going back to 2006 we find a Nature Biotechnology paper using hESC to make pancreatic progenitor cells that can turn into β cells and other kinds of pancreatic cells, work from a team led by Ed Baetge of Novocell (now ViaCyte). Only now is ViaCyte going to start their in-human trials. These things take time.
  • ViaCyte’s product is not pure β cells, while the Harvard product appears to be relatively pure β cells. This could prove to be an important advantage over ViaCyte’s approach in the long run.
  • A challenge for any stem cell-based product is potential immune rejection by the patient given that Type I Diabetes has an immune component as a disease and the fact that the product will be allogeneic.
  • What works in mice often doesn’t work in humans so caution is in order.
  • Whether talking about Harvard or ViaCyte or anyone else, it is way premature for the media to talk about “cures” for Diabetes. The most appropriate word to use is “treatment”.

 

More on Betatrophin, my take on the Cell paper, and a video

Betatrophin

UPDATE: Unfortunately the Betatrophin paper discussed here originally back in 2013 has now largely been proven to have come to incorrect conclusions (for more read this).

I finally got a chance to read the Cell paper by the Melton team on Betatrophin and it is quite cool.

I think one big question is whether this can this be translated into humans, but it seems very encouraging.

Another question is whether Betatrophin or some derivative when given as a chemical pill to patients could help control blood sugar. In other words, do we have a drug here? I hope so!

A final big question is the mechanism by which Betatrophin works as the authors conclude in the paper:

We do not yet know the mechanism of action for betatrophin. It may act directly or indirectly on b cells to control their proliferation. Identification of the betatrophin receptor and/or other possible cofactors will help to explain how the liver and fat interact with the pancreas to regulate b cell mass. Nonetheless, identification of betatrophin as a hormone that can exert control on b cell replication and b cell mass opens a new door to possible diabetes therapy.

Above Melton and his postdoc Peng Yi (see image at the top) discuss the discovery and give us a behind the scenes look at what went into in the video above.

How often do we get a window into the world of a big scientific discovery like this video? Very intriguing!