Posted by Ellen on June 02, 1999 at 19:37:47:
In Reply to: U. of Miami DRI Show me better news today posted by Mary E. on June 02, 1999 at 17:04:32:
This is from the DRI website: Has it already been posted? If so , I apologize. The researchers were very clear that this is just A STEP, no grandiose promises. But it looks promising that they could keep the monkeys healthy and the islets functioning well for over a year.
Diabetic Monkeys Off Insulin After Receiving Cells and Monthly Doses of
Experimental Drug
Study at Diabetes Research Institute Are Closest-To-People Findings Yet
A new drug that has shown promise in preventing organ rejection might be
the first drug to really work for diabetics waiting to receive
transplanted pancreatic cells, according to a study conducted at the
Diabetes Research Institute (DRI) at the University of Miami. In press
in the Proceedings of the National Academy of Sciences, the
investigation reports that six out of six diabetic monkeys that were
given anti-CD154 together with a transplant of insulin-producing cells
called islets, became insulin-independent after taking monthly doses of
the drug. In 3 cases, the animals remained insulin-free after
discontinuing therapy at one year post-transplant, and without
evidencing any of the toxic side effects that plague currently available
anti-rejection drugs. Such an advance could move islet cell
transplantation out of the experimental arena and into clinical practice
sooner rather than later.
"It's been the Holy Grail of islet cell transplantation to identify a
safe anti-rejection agent that works in a diabetes model that is closer
to human beings than a mouse," explains Norma S. Kenyon, Ph.D.,
associate professor of medicine and the study's lead author.
"Anti-CD154 is an immune system modulator that prevents rejection
without harming islet cells, and seemingly, without stunting growth, or
causing infection or cancer like traditional immunosuppressive agents.
As a transplant immunologist who's worked in this field for almost 20
years, and especially as the mother of a daughter with diabetes, this is
the most exciting development I've seen in a long time."
Using a two-stage system, T-cells or lymphocytes, enable our immune
system to ward off unwanted invasion, whether it be caused by viruses,
bacteria, or unknown cells. The first stage involves recognition that a
foreign body does not belong to the "self". The second stage, called
co-stimulation, results in the immune system's gearing up and involves
the production and activation of additional T-cells – a battle cry of
sorts. An immune system response, such as is seen in the rejection of
transplanted cells or organs, requires that both these steps take
place. AntiCD154 blocks the co-stimulation phase, thereby preventing
the destruction of the transplanted islet cells. "It appears that the
body may find other pathways to prevent infection, as these animals have
remained healthy without any sign of illness for over a year," concludes
Dr. Kenyon.
"In diabetes, the cells that produce insulin are destroyed by the
patient's own immune system. Islet cell transplantation attempts to give
back to these patients, the cells in the pancreas that produce insulin
and thus restore the body's ability to convert food into energy,"
explains Camillo Ricordi, M.D.,
Stacy Joy Goodman Professor of Surgery and Medicine and Scientific
Director at the DRI. "If there were a way to prevent rejection without
condemning an individual to a lifetime of toxic drugs, then
transplanting islet cells – given in a 25 minute, non-invasive procedure
- could become the treatment of choice," he continues. "AntiCD154 may
form part of that final solution."
The soon-to-be-published study entailed transplanting six diabetic
monkeys with islets from severely mis-matched donors while administering
four or 5 doses of antiCD154: on the day before, the day of, and on days
3,10, and18 post-transplant. Maintenance therapy was initiated on day 28
and given every 28 days thereafter. While an untreated control evidenced
rejection of transplanted islets as early as day 6 after transplant, all
six treated animals evidenced islet function which improved over time
after the first 3-4 months post-transplant, and eventually equaled a
non-diabetic condition. (One treated animal that received too few islet
cells required re-transplant, subsequently achieving and maintaining
insulin-independence 27 days after the 2nd transplant.) All animals
gained weight at par with other untransplanted colony mates, did not
show signs of infection, or significant immune system alterations. All
six animals continue to be insulin independent from 6 months to more
than a year post transplant. (In a related DRI study published last
week in Diabetes, Dr. Kenyon and her colleagues reported that antiCD154
is also capable of reversing individual episodes of islet cell rejection
if and when they begin.)
The DRI's narrow focus and record of progress in cure-related diabetes
research over the past twenty years has earned it the distinction of
becoming the National Institutes of Health's (NIH) only academic partner
in the new national transplantation initiative to cure type 1 diabetes
and its complications. The state of Florida, recognizing the need to
move Diabetes Research forward as quickly as possible, has give the DRI
$1.5 million from its fiscal year 1999/2000 budget towards Islet Cell
Transplantation.
Note: Copies of the study are available to members of the media through
the National Academy of Sciences' press office (202-334-2138, ms:
99-1968). Diabetes has made the related study available as a rapid
publication online at (http://journal.diabetes.org/diabetesrapids.asp.)
Additionally, Science covers this and other related CD154 research
in it's June 4th issue. Researchers wish to acknowledge the National
Institutes of Health (specifically the NIDDK and NIAID), Biogen, Inc.,
and the Diabetes Research Institute Foundation for their support of this
work. Interested members of the public can obtain more information by
attending the Diabetes Research Institute Foundation's A World of Hope
educational research conference scheduled for October in Miami.
Conference Information is available on this web site, or by calling
1-800-321-3437.