SAN DIEGO, Dec. 18, 2014 /PRNewswire/ -- ViaCyte, Inc.
announced today a preclinical study published online in Cell
Stem Cell that describes a novel approach to replace the
insulin-producing cells that are lost in type 1 diabetes. The
approach utilizes pancreatic precursor cells derived from human
embryonic stem cells and a pro-tolerogenic therapy that has the
potential to allow the cells to survive after transplantation into
the host without continuous immunosuppressive therapy. Type 1
diabetes results when a person's own immune system destroys
insulin-producing cells in the pancreas, and replacement of these
cells is thought to be an effective way to ameliorate the
disease.
The study, conducted by scientists at the University of California, San Francisco (UCSF) and
ViaCyte, a privately-held regenerative medicine company, documented
in a mouse model that a selective blockade of specific elements of
the immune system, co-stimulatory blocking agents CTLA4Ig and
anti-CD154, allows the implanted precursor cells to avoid immune
rejection and develop into the insulin-producing and other cells of
the healthy endocrine pancreas. These cells release
pancreatic endocrine hormones such as insulin in response to
changes in blood sugar.
Normally, cell transplants from an unrelated donor remain viable
only if the recipient's immune system is suppressed. The new
study, published online in advance of the February print edition of
Cell Stem Cell, utilized several models including a mouse
model that has been "humanized" in the sense that it carries key
parts of the human immune system and should respond immunologically
to the human cells as would occur after a transplant into a
patient, with a promising new technique to gently and selectively
dampen T-cell-mediated transplant rejection.
The approach allowed the implanted cells to grow, produce
insulin, and form islet structures. The mice, which were
treated to chemically eliminate their own insulin-secreting cells,
had healthy levels of insulin provided by the implanted human
cells, and consequently normal blood sugar levels. The study
authors believe that the approach, discovered in normal mice and
validated in the humanized mouse model, could be developed into a
method that combines cell therapy with the tolerogenic treatment
providing a "sustainable alternative strategy for patients with
type 1 diabetes."
The cells used in the experiments were similar to those
developed for use in ViaCyte's VC-01™ product candidate which is
currently being studied in the clinic. These pancreatic
precursor cells (called PEC-01™ cells) differentiate and mature
after surgical implantation into fully functioning
insulin-producing beta cells and other endocrine cell types that
make up the normal human pancreatic islet, the region of the
pancreas that contains insulin. The VC-01 combination product
employs a macroencapsulation device that is designed to protect the
implanted cells from the patient's immune system.
Normally, non-encapsulated PEC-01 cells would be immunologically
recognized as foreign and eliminated by T cells. However, in
the study described here, UCSF and ViaCyte researchers used an
emerging therapeutic strategy that stops the rejection process by
selectively blocking co-stimulatory signals that T cells must
receive in order to initiate rejection.
"The demonstration that these new immunotherapies block specific
pathways and immune cells that are responsible for attacking
pancreatic islet cells and prevent the rejection of implanted
PEC-01 cells is an exciting finding that could lead to advances in
the way we treat diabetes and other diseases," said Jeffrey
Bluestone, PhD, who holds the A.W. and Mary Margaret Clausen
Distinguished Professorship in Metabolism and Endocrinology at
UCSF. "In the future, a short treatment with immunotherapies
to produce tolerated immune cells could open the door to a wide
variety of practical regenerative medicine approaches."
Kevin D'Amour, PhD, chief scientific officer at ViaCyte
commented, "These findings, should they be verified in human
trials, could provide an alternative approach to the treatment of
type 1 and insulin-requiring type 2 diabetes with our PEC-01
cells. By interfering with the immune processes that normally
lead to recognition of foreign cells, these new immunotherapies may
represent a way for the implanted PEC-01 cells to survive and fully
mature to islet like structures, producing insulin and other
regulatory proteins in order to maintain normal blood sugar levels
long-term."
Over a million people in the United
States manage their type 1 diabetes with multiple daily
injections of insulin and rigorous management of diet and
lifestyle. Islet cell transplantation had been demonstrated
to reduce or eliminate the need for insulin injections, but at a
high cost: patients require strong immunosuppression for the
remainder of their lives, which carries significant side effects,
including risks of infections and cancer.
In related research, ViaCyte is currently evaluating the VC-01
product candidate, which is a combination of PEC-01 cells
encapsulated within an implantable device that shields the cells
from immune-system rejection. A Phase 1/2 clinical trial,
called STEP ONE, or Safety, Tolerability, and Efficacy of VC-01
Combination Product in Type 1, is evaluating the VC-01 product
candidate for the treatment of type 1 diabetes.
The findings in Cell Stem Cell suggest that immunotherapy
may be an alternative to the use of a physical protection device to
prevent immune system rejection of the PEC-01 cells.
A Disease Team Research Award and a Transplantation Immunology
Award, both from the California Institute for Regenerative Medicine
(CIRM), supported the research publication titled, "Tolerance
Induction and Reversal of Diabetes in Mice Transplanted with Human
Embryonic Stem Cell-Derived Pancreatic Endoderm."
About ViaCyte
ViaCyte is a privately-held,
clinical-stage regenerative medicine company focused on developing
a novel cell therapy for the treatment of diabetes. ViaCyte
is conducting a Phase 1/2 clinical trial of the Company's lead
product candidate VC-01 in patients with type 1 diabetes who have
minimal to no insulin-producing beta cell function. The VC-01
combination product is based on the production of pancreatic
progenitor cells (PEC-01), which are implanted in a durable and
retrievable encapsulation device, known as the Encaptra®
drug delivery system. Once implanted and matured, these cells
are designed to secrete insulin and other regulatory factors in
response to blood glucose levels. VC-01 combination product
is being developed as a potential long-term diabetes treatment
without immune suppression and without risk of hypoglycemia or
other diabetes-related complications.
ViaCyte is headquartered in San Diego,
California with additional operations in Athens, Georgia. The Company is funded
in part by the California Institute for Regenerative Medicine and
JDRF. For more information, please visit www.viacyte.com.
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