Wednesday, October 5, 2016

Quantum Leap in Diabetes Treatment

 I recently attended a talk on diabetes at Harvard, led by Doug Melton of the Harvard Stem Cell Institute. It was inspiring because they were talking about a cure, not just about some new drug or some new type of pump.

Melton has two children with type 1 diabetes, and after the talk, when I went up to thank him for his work, he said he's really driven to find a cure because of his kids.

The talk was titled A Quantum Leap in Diabetes Treatment, and Melton described how they can now take induced pluripotent stem cells (iPSCs) and transform them into beta cells. They use iPSCs instead of regular stem cells isolated from aborted embryos because President Bush restricted funding for stem cell research in 2001. One speaker said that move set back the research by about 10 years.

However, in the long run it turns out that using iPSCs instead of cells from aborted embryos has the advantage that you can use cells from your own body, which would be less likely to be destroyed by your immune system, although autoimunity can destroy your own tissues.

Melton said it's taken about 10 years to work out how to make beta cells from the iPSCs. First you have to tell the cells to differentiate into gut cells. Then into pancreatic cells. Then into hormone-producing pancreas cells. Then into beta cells. Each step in the process requires different chemicals, some small molecules and some proteins. Complex thought it is, they can now quickly make a lot of functioning beta cells in a test tube. Well, actually in flasks.

You can see the process here. Semma Therapeutics, which this links to, is named for Melton's two children Sam and Emma.

One thing emphasized at the talk was that this type of research requires cooperation among different specialists. Melton and his lab do the basic research, but they're not physicians and require the help of transplant surgeons like Sayeed Malek, of Harvard Medical School and Brigham & Women's Hospital. They also need engineers to scale up production of beta cells and pharmaceutical companies to produce large amounts of the substances used to transform the stem cells. They said that only in the Boston area can one find so many different specialists, so the cure is likely to be found there.

The first patients to get the new beta cells will be those who have had a pancreatectomy and who have very labile diabetes as a result, they said. This is because such people lack the autoimmune attack that is part of type 1 diabetes, so they can investigate one half of the puzzle without the other. This will be done next year, with only 10 patients.

The next step will involve patients who are already taking immune-suppression drugs, for example those who have had a kidney transplant.

Finally, patients with type 1 will get the cells, and eventually even those with type 2 whose beta cells can't produce enough insulin to overcome their insulin resistance. Clearly the cure will take time, but Melton said he's really optimistic about it.

Others who spoke and answered questions were Gordon Weir of the Joslin Diabetes Center, who was a teacher and mentor of Melton, Robert Millman of Semma Therapeutics, and Peter Amenta of the Joslin Diabetes Center.

Weir said this field is really accelerating. They're starting trials for spinal transplants and retinitis pigmentosa.

Someone said that cancer cells resist immune attack, and they're trying to find out how they do it, so this could be used with autoimmune diseases.

They're also trying to find a universal donor cell that would lack the triggers for autoimmune attack.

They said it will cost $1 million per patient to do the stem cell implants, so until they reduce the cost, they're probably not going to implant many patients.  However, they also noted that T1 is also very expensive, and will get even more so, and if you spent $1 million on a 6-year-old, you might recoup the cost through the kid's lifetime.

They noted that beta cells replicate very slowly, like brain cells. So each beta cell normally divides only 5 or 10 times in a lifetime, or 1/10,000 cells dividing per day. So just eliminating the autoimmune attack without beefing up the replication wouldn't help.
Again, I found it inspiring to hear people who know what they're talking about instead of the opinionated views one hears on the internet and the paranoid idea that big pharma will never contribute to a cure because producing the relevant drugs is so profitable. These people really want to find a cure.

I want that too.