New diabetes treatment would turn liver cells into insulin-producers
When pancreatic islet allo-transplantation therapy was first introduced, it provided hope for countless diabetics tired of daily insulin injections. While the technology has delivered on much of its promise, Tel Aviv-based regenerative medicine firm Orgenesis is currently developing a treatment of its own, that it claims addresses much of the shortcomings of islet therapy. In a nutshell, its approach involves converting the patient’s own liver cells into cells that produce insulin.
In type 1 diabetes, the pancreas no longer produces insulin – insulin being a hormone that removes excess sugar from the bloodstream. Typically, the missing insulin must be provided in the form of daily injections. With islet therapy, however, clusters of cells are transplanted from a deceased party’s donor pancreas into a diabetic patient. Known as islets, these cell clusters produce insulin within the body, so no injections are needed.
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Among the drawbacks to the approach, however, is the fact that a suitable donor pancreas may not be available. Even if it is, recipients need to stay on immunosuppressive medications in order to keep the islets from being rejected, and those medications can carry health risks and severe side effects of their own.
That’s where the Orgenesis system comes in.
It involves harvesting cells from the patient’s own liver, which are then propagated in the lab. A master control gene known as PDX-1 is then used to convert those lab-grown liver cells into what the company calls Autologous Insulin Producing (AIP) cells, which are similar in function to islets. The AIP cells are then introduced back into the liver via a catheter, where they set about producing insulin.
"The liver and the pancreas are closely related in function and have a shared site of origin in the embryo," said Scott Carmer, CEO of Orgenesis North America. "If you look at some primitive animals, there is only one organ that has the function of both the liver and the pancreas. Because they are so closely related, adding PDX-1 to liver cells causes a cascade of gene expression that changes the cells into pancreatic islet cells."
According to Orgenesis, the advantages of its technology include the fact that, because the patient’s own cells are used, there’s no shortage of donor material and no immunosuppressive drugs are necessary. It’s also said to be less costly than other approaches, requires no self-monitoring or other work on the part of the patient, and results in the production of insulin within just a few days of introduction of the AIP cells.
The system has already been tested on human liver tissue in the lab and on diabetic rats. It is hoped that human clinical trails may begin later this year. One thing that those trials may indicate, is how often the therapy will be required.
"We don't know for sure yet but our best estimate is a minimum of [every] 5 to 10 years," Carmer told us. "We plan on storing a portion of the cells so they don't need to be extracted again, but instead can be thawed and reintroduced to the patient if there's a need."