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”.

 

Great News: FDA Nod For ViaCyte IND of Diabetes Stem Cell-Based Product

VIACYTE, INC. LOGOType 1 Diabetes is a huge global problem.

Where are the solutions that would compliment or replace insulin therapy for diabetics?

There haven’t been too many that have gotten very far, which makes the news of a potential stem cell-based therapy moving along in the pipeline all the more exciting.

ViaCyte (see more posts here, here, here, here on the company) just got FDA approval for its investigational new drug (IND), paving the way to start a combined Phase I/II clinical trial. ViaCyte was one of four “good citizen” stem cell biotechs that I gave a shout out to in my book on stem cells.

The drug, VC-01, is an embryonic stem cell-derived product consisting of pancreatic progenitor cells (PEC-01 cells) delivered in a capsule (Encaptra device).

In mice, the product effectively treats a model of Diabetes and stabilizes blood sugar. Not too high and not too low. I really think there’s some hope here for human patients down the road with this and other similar kinds of approaches.

What Diabetic patients would be eligible for the trial? According to MarketWatch, about 40 patients with severe disease would be enrolled:

The Phase 1/2 clinical study will evaluate the VC-01 product candidate directly in patients with type 1 diabetes who have minimal to no insulin-producing beta cell function.  In addition to evaluating the safety of the product candidate in these patients, the study is designed to demonstrate the effectiveness of the VC-01 product candidate in replacing the lost endocrine function that is central to the disease.  In an open-label, dose-escalating format, ViaCyte expects to enroll approximately 40 patients in the study at multiple clinical sites.

You stock investors out there might be getting excited about ViaCyte, but unfortunately at present time it is a privately held company. This is one that even I, usually a very cautious investor, might consider buying the stock of if it goes public.

ViaCyte’s work has been funded by both CIRM and JDRF:

“We are pleased to have received FDA acceptance for our clinical trial protocol and look forward to initiating this study shortly” said Paul Laikind, Ph.D., President and Chief Executive Officer of ViaCyte.  “The commencement of this clinical trial marks a significant milestone for ViaCyte, as we begin studying the use of the VC-01 product candidate for the treatment of type 1 diabetes.  Instrumental in our ability to achieve this milestone are JDRF, the leading global organization focused on type 1 diabetes (T1D) research, and the California Institute for Regenerative Medicine, a leading organization focused on advancing stem cell research and regenerative medicine.  Both organizations have been strong supporters of the work we are doing at ViaCyte.”

This is a really big deal and a reason to cautiously have hope for the future of stem cell-based therapies for Type I Diabetes.

 

Harvard’s Doug Melton Blockbuster Discovery of Hormone Betatrophin: Possible Future Diabetes Treatment?

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).

Today Harvard Stem Cell Institute (HSCI) reported the discovery, in a paper in Cell by Harvard Professor Doug Melton, of a powerful new hormone called Betatrophin that can stimulate growth of beta cells in vivo. Beta cells are the type of cell that are lost in Diabetes.

From the HSCI press release:

The hormone, called betatrophin, causes mice to produce insulin-secreting pancreatic beta cells up to thirty times the normal rate. The new beta cells only produce insulin when called upon by the body, offering the potential for the natural regulation of insulin and a great reduction in the complications associated with diabetes, the leading medical cause of amputations and non-genetic loss of vision.

Of course, a big question pointed out by the team themselves is how this might work in humans including Diabetes patients:

“We’ve done the work in mice,” Melton says, “but of course we’re not interested in curing mice of diabetes, and we now know the gene is a human gene. We’ve cloned the human gene and, more over, we know that the hormone exists in human plasma; betatrophin definitely exists in human.”

“If this could be used in people,” said Melton, Harvard’s Xander University Professor and co-chair of the University’s Department of Stem Cell and Regenerative Biology, “it could eventually mean that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month, or in the best case maybe even once a year.”

I think is a huge discovery and I would think the odds are better than 50-50 that it will work in people.

A touching part of the press release mentions how Melton showed appreciation for his postdoc Peng Yi the morning after Yi had shown Melton evidence of the breakthrough:

The following morning, when Peng Yi sat down at his lab bench, there was a formal looking, cream-colored envelope lying on the brown surface of the bench. He opened it up, and took from the envelope a handwritten note from Doug Melton. It reads:

Dear Peng, I can hardly sleep – I am so excited by your result. It’s a tribute to your hard work and hard thinking.

Can’t wait to see the data from the repeat.

Doug

How cool is that?

I can’t wait to learn more about Betatrophin.