Last month I attended the ILSI Biomed 2011 Conference in Tel Aviv to learn about some of the exciting and promising diabetes-related research and development that’s taking place. I heard a fascinating presentation by Zohar Gendler, the CEO of Beta O2 Technologies, a biomedical company developing an implantable bio-artificial pancreas, the ßAir.
ßAir is the brainchild of Dr. Pnina Vardi, Director of the Laboratory for the Research of Diabetes and Obesity at Felsenstein Medical Research Centre at Tel Aviv University and Dr. Konstantin Bloch, head of the research team at the Diabetes and Obesity Research Laboratory, at Felsenstein Medical Research Center and a senior scientist in the Sackler Faculty of Medicine at Tel Aviv University. For years Vardi and Bloch worked together on islet cell transplants and they were continuously frustrated by the fact that immunosuppression, with its terrible side effects, was necessary to keep islet cells alive. Their frustration led them to encapsulation studies, where islet cells were placed inside a membrane that protected them from a host’s immune system.
The problem Vardi and Bloch faced in their studies was the same problem others working on a bio-artificial pancreas were facing- the encapsulating membrane was blocking more than just an immune response, it was also preventing oxygen from reaching the islets. Without an adequate oxygen supply, islets can’t produce insulin. They can’t survive.
To try to find a way to enable oxygen to reach the encapsulated islet cells, Vardi and Bloch conducted a number of experiments which led them to conclude that the best way for islets to receive oxygen would be via injection. They brought in engineer and veteran entrepreneur, Yossi Gross, who helped them develop ßAir, a device for implantation in humans. In ßAir, islet cells are placed within a unique protected device which enables glucose, oxygen, and insulin to flow in and out of the blood stream, while simultaneously preventing the entry of immune system’s antibodies and T-cells, which would destroy the islets. The device is implanted subcutaneously in a minimally invasive procedure, and oxygen is delivered to the islets via injection. With an adequate oxygen supply to satisfy metabolic needs, the islets can sense glucose levels and produce appropriate amounts of insulin.
I had the opportunity to speak to Dr. Vardi about her work, and Zohar Gendler kindly answered some questions about ßAir and the promise it holds.
How is your implantable pancreas different from islet cell transplants?
To try to solve the problem of immune system reactions, several companies are currently culturing islets within a device composed of a biocompatible membrane, a porous matrix that enables flux of materials in and out of the device. This allows for implantation without rejection. The amount of available oxygen in these devices, however, is limited, and the rate of oxygen consumption by the islets is faster than the supply. This leads to the death of the cells and they become incapable of producing insulin. This is where ßAiris different. No other company has a product which addresses both the problem of the immune system reaction and the problem of oxygen deprivation.
How does it work?
The ßO2TM implantable system is composed of two parts: (1) an immune protection unit which contains the islets of Langerhans (insulin-producing cells), immune protecting material and a membrane and (2) an oxygen supply unit based on daily oxygen refueling using table top injection system and an implantable port.
Where is the device implanted?
It’s implanted subcutaneously on the side of the abdomen in a quick, minimally invasive procedure.
Today islet cell transplants are rarely performed (due to lack of donor islet cells) and usually they’re only done in cases of “brittle” diabetes. Is your device intended for a wider group of diabetes patients?
Our device doesn’t need immunosuppressive drugs and for this reason it is applicable to all patients with type 1 diabetes. We don’t anticipate a problem with islet cell shortage. We plan to begin our trials with human donor islet cells and then move to pig islets. Pig insulin was used to treat diabetes in humans for many decades. It is only one amino acid different from human insulin, and the supply of cells is potentially unlimited. Later, we plan to use stem cells.
Could you explain why your device is a better solution for managing diabetes than an insulin pump and a continuous glucose monitor (CGM)? What does your solution offer patients that traditional solutions do not?
The primary limitation of the closed loop system with a continuous glucose monitor is the lack of portable and well calibrated continuous glucose monitoring. Even after the realization of the technology the patients will still need to replace the infusion set and the insulin container every few days, and live with an external needle connected to an external device. In addition, an insulin pump can release only insulin, but the pancreas and the islets in our device also produce glucagon. This means we provide a good solution to incidents low levels of blood glucose (hypoglycemia).
In your presentation you mentioned the daily oxygen injection required by the device to keep the islet cells alive. What does the injection involve? Would it restrict the life of the patient?
The patient will need a refueling process every 24 hours, which should take 2-3 minutes (net refueling time is 40 seconds). In this process, the patient injects oxygen into the device through an implantable port using the table top injection unit that we developed.
In regard to the encapsulation of the islet cells, what exactly is the semi-permeable layer that allows glucose and oxygen through but prevents immune rejection? What is it made of? I understand this is proprietary technology, but can you give us some detail?
This is a very challenging issue. We need to give a high level of protection to the islets against the host’s immune system and at the same time allow the glucose to go in and the insulin to go out. The immune protection compartment is built on the basis of two materials (two types of alginate) and a Teflon membrane. Alginate is a well known material, produced from algae, and we are using specific material with specific treatment to this material. The alginate protects the islets on the basis of natural negative electrical charging. The Teflon membrane stops the cells and the macro-molecule of the host’s immune system.
You have completed successful trials in rats and pigs. Could you tell us a little about the trials and about the results?
We conducted a long series of trials in small and large animals. In all of them the results are extremely positive. In typical study, the blood glucose (daily average) after device implantation was adjusted to near normal glucose level and returned to the disease state after the removal of the device (after 30-90-180 days). In this study we also found a significant reduction in HbA1c levels. We’ve also shown that when our device is removed after six months of implantation we can identify insulin and glucagon in the islets. This means that we have complete solution, a bio-artificial pancreas that can react to high and low glucose levels.
What’s next? When do you plan to start human trials?
We plan to begin the first human trial this year (2011) in Germany.
Assuming you are successful, when do you think this technology could be available (in the U.S. or Europe)?
We plan to achieve marketing approval in Europe in 2015 and in the U.S. in 2016.
Karmel Allison contributed to this interview.