diabetes

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Encapsulating answers to type 1 diabetes

People with type 1 diabetes are understandably excited about progress toward an “artificial pancreas” but they never lose the hope for a true cure, in which they can live like everyone else, without juggling synthetic hormones and hardware clomped on their skin that pierces their skin and will never work perfectly.

A true cure is a blue-sky goal built on two sets of major medical advances, and we have no idea what year those advances might arrive.

One set is to understand the autoimmune onslaught that brings on type 1 and then find a way to stop it. Serious and sometimes brilliant research keeps charging ahead, but autoimmune diseases hold extremely devious secrets and guard them very well.

The second set is to create a cells that replace those wiped out by the autoimmune attack and can generate insulin (and maybe related pancreatic hormones) at appropriate levels. Stem cell research aimed to do so is going gangbusters but is generally a long way from clinical trials.

With one big exception:

Yesterday Viacyte filed with the FDA for permission to run a trial for its VC-01 device, which encapsulates human progenitor cells—human embryonic stem cells that in this case have gone partly down the development path to hormone-producing cells. (The company, then known as Novocell, began work with embryonic stem cells years before the 2006 discovery of ways to create induced pluripotent stem cells, which possess very similar abilities to differentiate into almost any kind of cell but can be created from adult cells.)

Viacyte’s encapsulation container is a Teflonish cartridge about the size of a band-aid and thickness of a credit card, with holes too small for immune cells to enter but big enough to allow oxygen, glucose and other key ingredients to flow in and to allow insulin and other hormones to flow out.

The theory is that the capsule is inserted via an outpatient procedure, the immune system mostly ignores it, blood vessels build up to feed the cells, the cells are driven by signals within their fairly normal local human microenvironment to differentiate into a range of hormone-producing cells, the cells churn out insulin and its hormone cousins, and normal blood glucose levels and related metabolism are maintained. A functional cure, in short, for a year or two or three while the device functions properly.

This all works nicely in mice, but mice are not always man’s best friend in diabetes research. Investigators have struggled with encapsulation techniques for many years, and stem-cell-derived cells are unproven. The list of what could go wrong in the Viacyte trial is very long. Patients might reject the capsule. The cells might die quickly or slowly or never gather suitable blood vessels or fail in other ways. They might generate side effects that no one has imagined.

But Viacyte seems to have the science on its side and its head on straight and a good step-by-step plan. Assuming the FDA agrees, I don’t expect a home run in the first trial, but simply getting on base would be huge. And we should know within a year.

Viacyte Encaptra

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Smart insulin readies for trial

If you have type 1 diabetes, your body produces little or no insulin, and you survive on injections of synthetic insulin. You always have a little too much or too little insulin running through your blood, except for times when you have a lot too much or too little. Too much, and you may start to slide rather quickly toward serious wooziness and maybe unconsciousness. Too little, and you increase your risk of serious complications down the road.

Thus the appeal of the concept of “smart insulin”, an insulin derivative designed to automatically react to the level of blood glucose and adjust the amount of insulin released so that glucose levels remain in a healthy range.

Back in 1979, Michael Brownlee and Anthony Cerami presented one smart insulin approach in Science. There’s been plenty of research on the concept since then, but it has remained a concept.

In 2010, though, Merck announced plans to buy the MIT spinoff SmartCells for a purchase price that may eventually exceed $500 million. And last week at a Merck investor briefing, Roger Perlmutter, executive vice president and president of Merck Research Laboratories, noted that the company plans to move a smart insulin candidate based on SmartCells work forward into clinical trials.

At the briefing, Perlmutter displayed just one slide, showing that injections of a drug candidate called L-490 could maintain blood glucose levels at normal levels in dogs using smaller dosages than needed with regular synthesized human insulin, thus suggesting that L-490 indeed was releasing insulin only as needed.

Merck’s plan for a trial drew little attention outside the type 1 community, as the markets concentrated on other drugs headed for bigger markets sooner. But if smart insulin works it might radically improve treatment not only for the millions with type 1 diabetes but for the substantial group of people with type 2 diabetes who already use insulin among their other therapies.