Orgenesis' Sarah Ferber, Ph.D on Using a Diabetes Patient's Own Liver Cells as a Novel Source of Insulin
(Thomson Reuters ONE) -
Diabetes currently afflicts approximately 285 million people worldwide, about
6.4 percent of the global population. The World Health Organization projects
that this number is set to rise to 366 million by the year 2030.
According to the American Diabetes Association, 1.9 million new cases of
diabetes are diagnosed in people aged 20 years and older in 2010, an estimated
7.0 million Americans have undiagnosed diabetes, and another 79 million have
pre-diabetes. In addition, approximately 25.8 million children and adults in the
United States-8.3% of the population-have diabetes.
Several kinds of treatment for diabetes are currently available, but all of them
present specific drawbacks to the patient. For example, insulin therapy can
trigger everything from weight gain to hypoglycemia, and its administration must
be constantly controlled and monitored by the patient. A novel approach to this
problem is currently being pursued by a small biotech company named Orgenesis,
which initiated its approach by asking the following question: What if a
diabetes patient's own cells-extracted from his or her own mature tissue-could
be made to produce insulin, secreting the compound automatically when needed?
This particular variety of cell therapy is a form of what has been dubbed
"autologous cell replacement."
For years, the concept of harvesting stem cells and re-implanting them into
one's own body to regenerate organs and tissues has been embraced and researched
in animal models. The treatment being developed by Orgenesis consists of several
steps. First, a standard liver biopsy is taken from a diabetes patient in a
clinical center and sent to a laboratory. In the lab, the liver cells are first
propagated in vitro. Some of these cells are then manipulated with a therapeutic
agent (i.e., the "master regulator" PDX-1 that governs pancreas development, or
additional pancreatic transcription factors in adenovirus-vector) that converts
a subpopulation of liver cells into different cells with pancreatic islet
phenotype and function.
The therapeutic agent triggers a cascade of events, converting the cells into
"autologous insulin-producing" (AIP) cells. These cells now act similarly to the
beta cells that produce insulin in the pancreas of healthy individuals. Insulin
is not only produced, but also stored and secreted in a glucose-regulated
manner.
Back at the clinical center, the newly formed AIP cells are then transplanted in
a standard infusion procedure back to the patient's liver where they secrete
insulin. Since the initial liver cells were taken from the patient himself or
herself, there is no chance of rejection. Orgenesis has successfully tested its
technology in mice, rats and pigs, and is working toward initiating clinical
trials in humans.
The surprising capacity to activate pancreatic lineage in the liver was first
demonstrated in mice by systemic PDX-1 administration using recombinant
adenovirus gene delivery. PDX-1 plays a dual and central role in regulating both
pancreas organogenesis in embryo and beta cell function in adults. The capacity
of PDX-1 to direct pancreas development has been demonstrated in mature fully
differentiated liver in vivo, both in mice and in Xenopus, possibly via a
process called trans-differentiation. This describes an irreversible switch of
one type of differentiated cell into another differentiated cell.
AIP therapy seems to be safer than other options, as it does not alter the host
genome but only alters the set of expressed genetic information that seems to be
highly specific to the reprogramming protocol. In addition, no human organ
donations or embryo-derived cells are required.
This form of therapy, if proven to be workable in clinical trials, would provide
several advantages over other insulin-dependent diabetes therapies currently
being studied. First, it frees the patient from daily involvement in the
monitoring of blood glucose levels, numerous insulin injections and watching
food intake and exercise. Indeed, the body itself is now continuously
controlling blood glucose levels. In addition to avoiding the chance of
autoimmune rejection, the procedure is only minimally invasive.
In summary, the use of adult human liver cells for generating functional
insulin-producing tissue may pave the way to autologous implantations, thus
allowing the diabetic patient to be the donor of his or her own insulin-
producing tissue.
- - - - - - - -
This report is an expert briefing published by BioMedReports.Com.
Author Sarah Ferber, Ph.D. is Chief Science Officer and founder of Orgenesis
(OTCBB:ORGS), a development-stage company with a novel therapeutic technology
dedicated to converting a patient's own liver cells into functional insulin-
producing cells as a treatment for diabetes. She can be reached at
info(at)orgenesis.com.
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Source: BioMedReports via Thomson Reuters ONE
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Datum: 15.06.2012 - 03:53 Uhr
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