Lots of buzz last week about that exciting development in stem cell therapy: Novocell researchers in San Diego, CA, managed to control diabetes in mice using human embryonic stem cells. A first! Validating the concept that embryonic stem cells can be coaxed into becoming insulin-producing islet cells right inside a living organism -- rather than simply in a petri dish.
So how far off are we, really, from making this happen in humans?
Yesterday I was privileged to have a long talk with Dr. Camillo Ricordi, director of the Diabetes Research Institute in Miami, FL, who's quoted in the New York Times coverage. He was actually a bit exasperated that he'd spent such a chunk of his time on the phone with the NYT reporter, explaining all the workings of the science, only to find himself quoted in one single sentence: "For those who say there is not much evidence that embryonic stems cells can cure diabetes, there you go."
Well, he got a chance to explain a whole lot more to me:
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As the NYT notes, the FDA may be hesitant to approve trying this therapy in humans because it involves injecting people with "early-stage" cells that have yet to "mature" in the body.
"Once you put these cells in vivo they can grow in any direction. In this study, there was also a tendency toward hypoglycemia. Maybe the cells will have 'shutdown problems.' Glucose levels in the 40s and 50s are of course not good," Ricordi says.
There's also that issue of developing tumors, which some of the mice did. Ricordi says the risk is 15%, which sounds far too high for most patients' taste, I'd imagine.
ROADBLOCKS & ALTERNATIVES
Just a few days before Novocell's announcement, Dr. Douglas Melton's stem cell group at Harvard published a paper in which they were able to "map human embryonic stem cells for differentiation," Ricordi says. This means they used screening tools to show that only a very few have the potential to become insulin-producing pancreatic cells.
This explains why others have not had success curing diabetes in mice using similar protocols; they simply weren't using the right stem cell lines, according to Ricordi. But the right stem cell lines are going to be very hard to come by.
"With only 6,000 donors a year, and only half of those suitable for this use, you could cure a max of 3,000 patients a year at best. But who's going to pay for this? Once this treatment became available without the need for lifelong immuno-suppressant drugs, it would become like the lottery -- everybody would want it. We don't want this to be some privilege restricted only to the wealthy."
He also says that human islet transplantation will be widely available much earlier than stem cell therapy. Islet transplantation from a healthy pancreas source is already in Phase 3 trials for FDA approval, he says.
The big issue with islet cell transplantation -- and stem cell, too, when it's ready -- is the need for immuno-supressing drugs that keep the body from rejecting the implanted material. These drugs have proven toxic to the implanted cells. "They block the capability of the cells to replenish themselves, to regenerate... but we've changed the mix of drugs, using a different combo of drugs that have less effect on the cells ability to replenish themselves," Ricordi says.
For stem cell treatment, Ricordi and the DRI are working on another option to eliminate the risk of the cells developing into tumors or other unwanted material in the body. They're developing so-called "suicide genes." They would use genetic engineering to pre-program genes to self-destruct in case they don't develop in a certain way. Pretty neat! The genes that go bad would just automatically commit suicide. Sound far-fetched? Scientists have been working on it for cancer therapy for at least a decade.
In any case, the Novocell announcement is exciting to the science world, and therefore to us, at a very fundamental level. "Before, there was no evidence that stem cells can cure anything," Ricordi says. "Hopefully the lessons we've learned from islet transplantations will help in this effort."
Thank you, Dr. R, and a huge thanks to the DRI for the work you all do!