Grant paves way to finding potential cure for Type 1 diabetes
The National Health and Medical Research Council (NHMRC) today
announced that The Garvan Institute of Medical Research would receive
over $15.7 million in various Research Fellowships, Project Grants,
Equipment Grants, Infrastructure Grants and a large Program Grant,
alone worth over $3 million.
The Program Grant, a joint initiative between the NHMRC and the
Juvenile Diabetes Research Foundation (JDRF) in Australia, has been
awarded to Dr Shane Grey, head of Garvan’s Gene Therapy and
Autoimmunity Group, to undertake a vital aspect of Type 1 diabetes
research. He will examine the action and function of insulin-producing
pancreatic ‘beta cells’ in clinical procedure known as ‘islet
transplantation’. Dr Grey aims to improve the success rate of
this procedure, a potential cure for Type I diabetes.
‘Islets of Langerhans’ are clusters of different types of cells in the
pancreas, including the beta cells that make insulin. Each pancreas has
around 1 million islets, which maintain the body’s blood sugar levels
in exquisite balance. A transplant involves removing the islets from a
deceased donor pancreas - and transplanting them into a
recipient.
“Around the world, over 100 transplants have been done, the most
successful by a team in Canada,” said Dr Grey. “The latest figures show
that after one year, there’s about a 70% success rate, the measure of
success being complete insulin independence. Sadly, after 5 years that
figure drops to around 10%.”
“Some people see that decline of beta cell function as failure.
Personally, I see a reason for optimism. We shot for the moon and we
got half way there. Now we have to figure out how to achieve the rest
of the journey, how to change the 10% into 100%.”
In Australia, approximately 100,000 people have Type 1 diabetes, an
autoimmune disease that usually starts in childhood. Over 40% of people
with Type 1 diabetes suffer from complications in later life that can
lead to renal failure, blindness or amputation. The most damaging
aspect of the disease is hyperglycemia, or very high blood sugar
levels, owing to an inability to produce insulin, the hormone that
helps convert glucose in our blood to energy in our muscles.
While the advent of easily injected insulin saved, and continues to
save, many lives, the effect is imprecise. The United Kingdom
Prospective Diabetes Study (released in 1999) and The Diabetes
Complications and Control Trial, undertaken by The U.S. National
Institute of Diabetes and Digestive and Kidney Diseases (between 1983
and 1993) demonstrated conclusively that hyperglycemia causes the
long-term blood vessel and tissue damage that occurs in diabetes. When
people were put on very strictly controlled dietary and insulin
regimens over a long period, the damage was markedly, but not totally,
reduced. The kind of precise (second-by-second) monitoring required to
completely prevent damage is impossible to achieve by insulin or
dietary control. Islet transplants offer a means of regaining the
body’s own perfect control over insulin production.
In Grey’s opinion, the secret to transplant success lies in the beta
cell, with one option being gene therapy. “We need to find a way to
modify the beta cell genetically so that it will survive the
transplantation process and allow recipients to produce their own
insulin. If we succeed, it will save a lot of suffering globally and
save billions of dollars in health budgets.”
“The NHMRC Program Grant gives us the opportunity to pool the thinking
of all the current Australian experts in this field, clinicians and
researchers, to try and figure out how to make islet tissue transplants
work in patients with Type 1 diabetes. The major hurdle to be overcome
is the fact that beta cells don’t like being extracted out of the
pancreas. When you transplant into a recipient, it’s estimated that up
to 70% will die within the first 24-36 hours. They are very fragile –
not like a heart, which you can put in a freezer box and ship across
the country.”
To achieve the aims of the program, Dr Grey has assembled an
outstanding team of senior researchers from around the country,
including Garvan experts, Associate Professor Trevor Biden, Dr Jenny
Gunton and Dr Ross Laybutt. In addition to Garvan researchers, the
program team includes senior members Associate Professor Chris Nolan
from the Australian National University (ANU) and Dr Sof Andrikopoulos
from Melbourne University.
“The JDRF in Australia, together with the NHMRC, have established a
smart system,” said Grey. “They’ve set up clinical islet transplant
centres around the country – a sort of clinical flagship program. Now
they’re feeding information to those centres through research programs
such as ours. It’s very collaborative and very exciting. In my opinion,
it’s the only way to make progress in a complex area such as this.”
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