In a person with diabetes, the insulin producing beta
cells in the pancreas are attacked by the immune system and destroyed, this
leads to a deficiency of insulin and high blood sugar (glucose).
People with insulin-dependent diabetes (all of type-1 and
about 27 percent of type-2 diabetics) lack the necessary amount of insulin in
their bloodstreams. This can, and often does lead to irreversible damage to
their hearts, blood vessels, eyes, kidneys, skin, feet and hearing.
Diabetes is not considered a high mortality condition,
but it is a major risk factor for other causes of death and has an extremely
high attributable burden of disability, for example; two percent of people
with diabetes become blind and roughly ten percent develop severe visual
impairment, fifty percent of people with diabetes die of cardiovascular
disease.
There is no cure for diabetes. The Standard of Care for
patients with reduced or missing critical hormones or proteins, such as
insulin, is often monitoring and injecting these proteins multiple times a
day.
Edmonton Protocol
Paul Lacey was a researcher at Washington University
when, in 1972, he cured/restored normoglycaemia in some diabetic rats by
transplanting islet cells (clusters of thousands of endocrine cells that
include beta cells that produce insulin) from healthy rats into the livers of
some diabetic rodents.
Over the next two decades researchers made hundreds and
hundreds of attempts to apply the procedure to humans. Unfortunately no one
was successful. By the early 1990’s most scientists had come to the
conclusion that islet-cell transplantation was a lost cause.
Dr. James Shapiro, Dr. Jonathan Lakey and colleagues from
the University of Alberta in Edmonton developed the Edmonton Protocol in the
late 1990s.
The Edmonton Protocol is a method of implantation of
pancreatic islets into the portal vein (a large vein returning blood
from the abdomen to the liver), of the recipient's liver.
The first patient was treated in March of 1999. The
protocol was published in the New England Journal of Medicine in July 2000.
Considerable excitement was created by the report - the first seven patients
were still insulin-independent after an average of 12 months.
How it works
Researchers use specialized enzymes to remove islets from
the pancreases of recently deceased adults. The islets are then purified and
counted.
Each transplant patient receives islets from one to three
donors. X rays and ultrasound guide the placement of a thin, flexible tube
called a catheter through a small incision in the upper abdomen and into the
portal vein. The islets are then infused - pushed - slowly into the liver
through the catheter.
The islets are kept from being destroyed by the
recipient's immune system through the use of two immunosuppressant drugs as
well as an antibody drug specifically used in transplant patients.
Once implanted, the beta cells in the transplanted islets
begin to make and release insulin. However full islet function and new blood
vessel growth from the new islets takes time so transplant recipients usually
need to take insulin injections until the islets are fully functional.
Since 2000 several hundred people have received islet
transplants – but by five years after the procedure, fewer than 10 percent of
all patients are free of daily insulin supplementation.
Obstacles to Edmonton Protocol
The shortage of islets is a significant obstacle, organ
donor rates are generally very low and especially so in Canada.
Unfortunately, many of the pancreases that are donated are not suitable for
extracting islets because they do not meet the selection criteria and islets
are often damaged or destroyed during processing. The number of islet
transplants that can be performed each year is therefore limited by a severe
shortage of suitable islets.
Immunosuppressive medications have significant side
effects and long-term effects are still not fully known. Immediate side
effects may include mouth sores and gastrointestinal problems - an upset
stomach and diarrhea.
Patients may also suffer from:
- Increased blood cholesterol, or blood
fat, levels
- High blood pressure
- Anemia
- Fatigue
- Decreased white blood cell counts
- Decreased kidney function
- Increased susceptibility to bacterial
and viral infections
- Increased risk of developing certain
tumors and cancers
Unfortunately the autoimmune response that
destroyed the transplant recipients' own beta cells in the first place can
happen again.
There are issues with infusion of islets into the portal
vein, an immediate blood mediated inflammatory reaction (IBMIR) causes over
50 percent of islets to die within hours or days following infusion into the
blood.
Another issue is that the liver site is associated with
islet transplant related procedural complications including catheter-induced
hemorrhage and thrombosis. Additional inhibiting factors include difficulty
in imaging the islets, an inability to remove the transplanted islets and the
limited number of islet transplants a patient can receive.
The State of Islet Transplantation today
From the report ‘Improvement in Outcomes of Clinical
Islet Transplantation: 1999–2010’ the author found on
diabetesjournals.org comes the following…
“Allogeneic islet transplantation offers a minimally
invasive option for β-cell replacement in
people with type 1 diabetes complicated by recurrent severe hypoglycemia
and/or marked glycemic lability.
Before 1999, less than 10% of islet transplant
recipients achieved insulin independence. In 2000, the Edmonton Protocol for
islet transplantation achieved insulin independence in seven consecutive
participants who received islets from more than one donor under a
steroid-free immunosuppression regimen. After this proof-of-concept success,
islet transplant programs expanded in North America and elsewhere. These
centers have offered evolving strategies of islet preparation and
immunosuppression, although the limited resources available have prevented
anything but independent Phase I/II attempts to standardize processes,
achieve success, and stabilize outcomes.
Even in the absence of insulin independence, an islet
transplant can protect type 1 diabetic recipients from severe hypoglycemic
episodes as long as residual islet graft function is maintained, as proven by
restoration of C-peptide production. Despite this compelling rationale, islet
transplantation for type 1 diabetes has produced variable success and elusive
durability, has frequently required multiple donor organs, and has balanced one
disease load - severe hypoglycemia - with another - long-term
immunosuppression.”
A search has been on for an alternative site for islet
transplantation as well as for an optimal medical device in which to implant
the islets. Several subcutaneous devices have previously been developed for
islet transplantation but from a preclinical and clinical perspective the
results from these products have been generally disappointing.
Current cell therapy is limited to poor cell survival,
inappropriate delivery of hormones, a lack of available donors and cells.
Sernova Corp. TSX.V – SVA
Sernova Corp is a Phase I/II clinical stage company
developing medical technologies for the treatment of chronic debilitating
metabolic diseases to replace proteins or hormones in short supply within the
body.
Sernova is currently developing two novel and closely
integrated, proprietary platform technologies.
The first proprietary platform technology is the Cell
Pouch System™.
Sernova’s Cell Pouch System™ is a versatile and scalable,
first-in-class implantable medical device made entirely of FDA approved
materials. The Cell Pouch System™ provides a natural “organ-like” environment
rich in tissue matrix and micro-vessels. This is the ideal environment for
therapeutic cells to thrive which then release proteins and/or hormones as
required. The Cell Pouch System™, being thin and typically smaller than a
business card, fits easily under the skin with virtually no visibility.
Due to the enormous market and potential for
significantly improved patient treatment Sernova’s first product focus is on
diabetes - islet cell transplantation is the only known therapy that can
reduce or eliminate the side effects associated with this chronic disease.
At this time there is no approved device to house and
protect therapeutic cells transplanted into a patient. The Standard of Care
for patients with insulin-dependent diabetes is monitoring and injecting
insulin multiple times a day.
Think of the Cell Pouch System™ as a potential natural
insulin producing pump with the added benefit of fine-tuned glucose control
with no need to replenish the insulin. When placed under the skin and filled
with islets it develops pancreas-like characteristics taking over normal
glucose control. A key feature of the device is its ability to develop tissue
matrix and natural micro-vessels, thought to be essential for the long-term
survival and function of therapeutic cells.
The second proprietary platform technology is Sertolin™ -
a cell-based technology providing an immune-privileged environment for donor
cells which reduces or eliminates the need for anti-rejection drugs.
Sertolin, when combined with therapeutic cells, protects
them from attack by the immune system. The combination of these protector and
therapeutic cells leads to long-term functional survival of the therapeutic
cells without drug therapy. The Sertolin™ technology has the potential to
reduce or eliminate the need for expensive lifelong daily anti-rejection drug
cocktails that make subjects susceptible to serious infections.
Cell Pouch System™ Phase I/II Human clinical study to treat Type-1 diabetes
In September 2010, following an extensive review of
Sernova's preclinical data, Dr. Shapiro MD, Ph.D. FRCS (Eng) FRCSC joined
Sernova Corp's Scientific Advisory Board.
On August 16th 2012 Sernova, and the University of
Alberta, announced the treatment of the first patient with insulin-producing
islets transplanted into Sernova's Cell Pouch System™ in a Phase I/II
clinical study to treat Type-1 diabetes.
The clinical study is being led by Dr. James Shapiro,
Professor of Surgery and Medicine, University of Alberta and Director,
Clinical Islet Transplant Program.
Sernova announced, on September 26th 2013, results from
the ongoing Cell Pouch System™ Phase I/II clinical study.
"We are really encouraged by the initial results
of this ground-breaking study. The preliminary findings that human islets
survive under the skin within the Cell Pouch pave the way for our ongoing
studies in patients that will now test how effective this new approach will
be. Importantly, the islets were shown to be residing within a natural tissue
matrix in the device, and were nicely integrated with micro-vessels, and
stained for insulin, glucagon, somatostatin and polypeptide at the 30 day
time point." Dr. James Shapiro, principal
investigator Sernova Cell Pouch System™ Phase I/II clinical study
Efficacy results are expected from the Cell Pouch System™
Phase I/II clinical study early in 2014.
An enabling platform
Sernova is exploring the additional utility of the Cell
Pouch System™ as an enabling platform for a range of therapeutic cell types.
The technology could be used for a patient’s own cells (autograft), or a
donor’s cells (allograft).
The therapeutic Cells placed into the device may also be
cells that can be a source to treat millions of patients such as stem cells
(stem cells have the ability to differentiate into other cell/tissue types)
or xenogeneic (derived or obtained from an organism of a different species)
cells. Sernova is talking to stem cell companies and suppliers of porcine
(pig insulin is almost identical to human insulin with the exception of one
amino acid) cells to ultimately expand the supply of islet cells that the company
can use to develop its therapy.
Sernova’s products are also designed to allow for multiple market expansion
opportunities within each therapeutic area. For example, the technology would
be beneficial if it provided a simple reduction in the number of daily
therapeutic injections a patient must take; however, there is the possibility
that it could even essentially ‘cure’ the disease through natural release and
regulation of the therapeutic proteins or hormones.
The Cell Pouch™ could be used for any chronic disease
where a deficient or missing protein or hormone can be replaced by
therapeutic cell transplantation.
Sernova has recently announced a collaboration with
Medicyte GmbH to develop a product for Haemophilia.
“Sernova is unique in having the only proprietary
human scalable technology solution for therapeutic cells which can thrive
within its Cell Pouch™ in a natural tissue matrix rich in blood vessels and
protected by Sertolin™ from immune system attack.” Dr. Philip M. Toleikis BA, MSc, PhD President and CEO Sernova
Corp.
Sernova’s current targeted markets
Cell therapies can cost $10,000 each and the Cell Pouch™
is thought to have a cost of $10,000, more study is needed as trials progress
but SVA’s total product combination could bring in as much as $30,000 to
$50,000 a patient.
Diabetes
Worldwide expenditures on insulin are estimated to be
over U.S. $15 billion annually. Total costs of diagnosed diabetes in the
United States was $245 billion.
About 347 million people worldwide have diabetes. The
World Health Organization (WHO) projects that diabetes will be the 7th
leading cause of death in 2030.
Haemophilia
Patients with hemophilia A have a defective factor VIII
gene. Currently, the number of people with hemophilia in the United States is
estimated to be about 20,000, an estimated 400,000 people worldwide are
living with hemophilia and only 25% receive adequate treatment.
Patients receive prophy-laxis factor replacement therapy
two to three times a week. Prophylactic therapy (prevention therapy) involves
three infusions of Factor VIII each week at the hospital at a cost of about
$260,000 each year.
The broader hemophilia market was $8.5 billion in 2011
and is expected to grow to $11.4 billion in 2016.
Conclusion
The holy grail of diabetes and hemophilia A treatment is
for patients not to have to take injections or infusions.
Next year, 2014, could be a break-through year for SVA,
its technologies and for diabetes and hemophilia sufferers.
"The findings in these initial patients parallel
the results in Sernova's multiple small and large animal safety and efficacy
studies of the Cell Pouch. These showed an exemplary safety profile, and that
islets were well- vascularised with microvessels and produced insulin. In
addition, the islet-rich Cell Pouches then went on to show long-term glucose
control in the diabetic animals." Dr. David
White, Professor Emeritus and Chair of Sernova's Scientific Advisory Board
talking about Sernova’s September 26th 2013, results from the ongoing Cell Pouch
System™ Phase I/II clinical study
Here’s how I think things are going to play out for
Sernova over 2014 and beyond:
- Board appointments
- Cell Pouch System™ Phase I/II clinical
study efficacy results
- In-house licensing deals with major
universities
- Regional licensing deal
There is no market cycle for drug, bio-technology and
bio-med device stocks. The need is always there and demand is growing at an
alarming rate while at the same time big pharma’s number of patents and
pipeline of new devices and drugs has fallen off a cliff. This “patent cliff”
has shifted the playing field so much so that any new and exciting drug or
device will be snapped up at a much earlier stage than previously thought
possible.
Sernova Corp. (TSX.V-SVA) and it’s Cell Pouch System™
human trial PhaseI/II clinical study efficacy results should be on everyone’s
radar screen. It’s definitely on mine.
Is Sernova on your radar? If not, it should be.
Richard Mills
Richard is the owner of Aheadoftheherd.com and invests
in the junior resource/bio-tech sectors. His articles have been published on
over 400 websites, including:
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