Current & Planned Research
“We could realistically see the Islet Sheet technology go to clinical trials within two years if we find proper funding and continue on the track that we’re on.”
—Jonathan R.T. Lakey, PhD, co-leader Islet Sheet Project research team, in 2010
Improving the Islet Sheet Design
Since the project team resumed intensive research in 2008, many improvements have been made to the Islet Sheet. For example, Dr. Lakey wanted to refine its handling properties, and with a few process changes Islet Sheet Medical produced a sheet that performed surgically as requested. ISM also compared its alginates with commercial versions to ensure that its proprietary formula works best.
Working with rats, which are known for sensitivity to implants, brought further refinements in sheet fabrication needed to fend off an aggressive fibrotic response.
Advanced imaging equipment at Dr. Lakey’s UC Irvine lab enabled the team to view sheets in impressive detail and resolution. They could investigate key characteristics, such as surface smoothness, within minutes of making new sheets, without animal implants.
Although the current Islet Sheet design is virtually ready for clinical use, we expect even further refinements to emerge from large-animal trials.
Studies with Small Animals
Our work with rats and mice has demonstrated that the Islet Sheet is well tolerated in small animal models. Both allografts (islets transplanted from and into the same kind of animal) and xenografts (islets from a different species) have been used. Islets in the sheets remain alive and functioning for days, weeks, and months—both in culture and when implanted into small animals. Studies with small animals continue at UC Irvine.
However, small animals such as rats have a very different insulin physiology than large ones such as pigs, dogs, monkeys—and humans. Studies with larger animals are crucial to show how well the Islet Sheet can normalize metabolism in creatures more like ourselves. And to show how well it passes the autoimmunity test—that it, keeps islets alive and working in these animals.
Large-Animal Trials—A Definitive Step
Large-animal studies will begin in January 2012 at the Cedars-Sinai Diabetes and Obesity Research Institute in Los Angeles, and we expect them to run between one and two years.
Professor Richard Bergman was asked to help design experiments. Based on his own successes with type 2 diabetes research, he recommended the canine model. The dog’s pancreas is carefully removed to produce the metabolism of type 1 diabetes, and replaced with Islet Sheets containing harvested canine islets. Dr. Lakey will share the leadership of these studies with animal physiologist Dr. Marilyn Ader, a longtime associate of Dr. Bergman.
Among the questions the studies will answer are:
- The best site to implant Islet Sheets
- The dose of islets required
- For how long transient anti-inflammatory drugs will be needed, and what type
- Islet function over time
Because the dog’s metabolism is close to our own, we should need consistent positive results from only about half a dozen animals to be assured that the Islet Sheet will work just as well in humans.
See Large-Animal Studies for more detail.
Clinical Studies—The Research Grail
Clinical trials will take place when the device is proven in diabetic animals. (The FDA has already approved clinical investigation of first-generation encapsulated islets.)
In this phase, projected for 2013, Islet Sheets containing human islets (allografts) will be implanted into people with type 1 diabetes. The first few patients will probably get a low dose, with the dose rising in later patients. The ultimate goal, of course, is good blood sugars without injected insulin. (For a preview of how a patient will experience Islet Sheet therapy, see What Happens in Islet Sheet Therapy?)
While clinical trials will use islets from human donors, the limited supply of such islets means that the cost of bringing the device into medical use must remain very high and the market small. So the project will simultaneously pursue research on xenografts (for example, pig islets) and cells grown in culture or genetically engineered. These methods have the potential to produce fully functional, immunologically human islets at a lower cost. We are already in collaborative studies with organizations producing such islets and cells.
- The design of the Islet Sheet has been continuously improved based on research results, especially since 2008, and the current version is near-ready for clinical use.
- Experiments with small animals have produced valuable results on the Islet Sheet’s biocompatibility and functioning.
- In fall 2011 the Islet Sheet will be tested in larger animals, whose metabolism is much more like that of humans. Clinical trials will follow, and the project is investigating new sources of islets.