Within the seek for a cure for type 1 diabetes, many scientists and researchers have converged around one general approach: the implantation of laboratory-grown islet cells which have in some way been shielded or hidden from the immune system. But the precise details of this potential cure are removed from settled, and many alternative groups are attacking the answer from different angles. It’s quite possible that an actual functional cure — if we ever get one — will mix innovations from several different labs that aren’t working together today.
Sernova, a Canadian biotech firm, hopes to contribute with its Cell Pouch System, a medical pouch that might be surgically implanted under the skin to accommodate implanted pancreatic islet cells. The Cell Pouch, ideally, will allow transplanted cells to raised integrate with the body, offering higher safety and efficacy. CEO Cynthia Pussinen walked Diabetes Day by day through Sernova’s innovation.
There hasn’t been much buzz about Sernova within the media, but the corporate can boast of some impressive results. “We’ve patients who’ve been insulin-independent for near 4 years,” says Pussinen.
Islet Cell Transplants
The islet cells, also referred to as the islets of Langerhans, are the parts of the pancreas that produce hormones. Islet cells are really cell clusters, not individual cells. These clusters are where you’ll find the beta cells, the insulin-secreting cells which can be destroyed within the autoimmune attack that causes type 1 diabetes, and a number of other other forms of endocrine cells which can be critical for correct metabolic function.
We all know that islet cell transplants can work. Some transplant recipients have remained freed from insulin therapy for a few years following the procedure. However the procedure is related to a wide range of issues which have prevented its widespread adoption as a therapy for type 1 diabetes:
- As of today, all islet cells should be harvested from the bodies of deceased organ donors, strictly limiting the provision.
- Transplant recipients require antirejection drugs for his or her latest cells from the immune system. These drugs have a severe side effect profile and are toxic to the transplanted cells.
- The transplants don’t at all times work: Many patients experience only short-term advantages.
The cell pouch is usually intended to unravel the last of those problems, which could help make islet cell transplants simpler and reliable and subsequently more viable.
Introducing the Cell Pouch
The cell pouch is an actual pouch that’s inserted under the skin of the abdomen. “It’s concerning the size of a bank card, only a number of millimeters thick, product of a really flexible polypropylene material,” says Pussinen. “We put the islet cells into the cell pouch. Patients report that they’ll’t even feel it.” The surgery only takes about quarter-hour.
The cell pouch’s materials have been approved by the U.S Food and Drug Administration for everlasting use within the body. One very early Sernova volunteer has had a cell pouch of their body for 14 years with no ailing effects. “You don’t see any fibrosis [scarring] of the tissue; the tissue across the pouch has remained healthy,” says Pussinen.
The cell pouch is meant to be an alternative choice to the prevailing approach to implanting islet cells directly into the portal vein, which allows them to settle within the liver. With this, the dominant protocol, “they don’t have long-term survival or engraftment in lots of cases,” says Pussinen. “And that is where the cell pouch is sort of different.”
The cell pouch doesn’t just sit there underneath your skin; the body actually grows around it, spreading blood vessels across its surface: “It becomes highly vascularized, it’s form of just like the roots of a tree growing around it. It forms a really nice home for the islet cells.”
“This can be a rather more stable approach. It’s safer; it’s tolerated much better.”
One other advantage of the cell pouch is that it may well be removed. This has already happened once after it was learned that a single study participant had received a transplant of islet cells that were contaminated with candida albicans yeast. (This happens sometimes. Organs for donation can’t be perfectly evaluated for sterility before transplantation occurs). The transplant team was capable of explant the cell pouch with none problems.
“It’s one other big profit: If something does occur, you’ll be able to take it out. With injections into the portal vein alone, once those cells are in there, you’re not getting them out. If something’s bad, you’re stuck.”
The Results
The early results suggest that the cell pouch system may improve the outcomes for individuals with type 1 diabetes undergoing islet cell transplants. Sernova recently announced the interim results from its Phase 1/2 trial of the system: Six patients have been successfully implanted with the cell pouch system.
- Five of those six are actually insulin-independent.
- All six have achieved A1C values within the nondiabetic range (lower than 6.5 percent).
The outcomes are even higher than Sernova expected; this early trial was designed only to evaluate the protection of the pouch system. Patients in a second cohort have been implanted with a higher-capacity pouch to assist determine optimal dosing.
Pussinen says that islet cell transplants could develop into a significantly better alternative than the establishment of insulin injections for individuals with type 1 diabetes: “Insulin therapy is admittedly, in my view, an incomplete approach. You’re not addressing the alpha cells or the delta cells, glucagon, or somatostatin. With islet cell therapy, this can be a very holistic approach and may achieve what we call a functional cure.”
The Future
The cell pouch still has many hurdles to leap, and is actually years away from FDA approval, if it gets there. And even when latest larger studies confirm the pouch’s positive effects, there’s still loads of work to be done.
While the cell pouch may help solve one issue related to islet cell transplantation, it doesn’t yet solve the others — the necessity for immunosuppressive drugs and the limited supply of organ donors. Due to these issues, islet transplants are currently limited to only essentially the most desperate cases, typically those with severe hypoglycemia unawareness and a history of dangerous hypoglycemic events.
Sernova has plans to deal with each problems.
The corporate has partnered with Evotec, a German firm that works with induced pluripotent stem cells (iPSCs). An identical approach has proved very successful for Vertex Pharmaceuticals, the business that’s widely acknowledged to be the closest to a kind 1 diabetes cure. These cells are grown in a laboratory and might be induced to develop into islet cells, which might allow Sernova to stop counting on organ donors. Lab-grown islets can be frozen for transportation, removing the necessity for helicopters, ambulances, and special couriers to move organs for transplant.
The cell pouch system doesn’t, in and of itself, reduce the necessity for immunosuppressive drugs, however it could help make it easier to guard transplanted islet cells. Sernova is currently laying the groundwork for implanting islets which have been “microencapsulated” in a conformal coating that might offer immune protection. Pussinen calls it a style of “shrink-wrapping.”
Immunosuppression has been called the ultimate piece of the puzzle of a kind 1 diabetes cure. Vertex is currently experimenting with its own encapsulation technique, but its success is much from assured.