A Reasearch Update
Found this at the JDF site- thought it was interesting. I have also
recently read an article about a new ecapsulation that has worked in
mice which protects transplanted islet cells from the immune system,
meaning there is no need for immunosuppressants.
Update: JDRF Harvard Center’s Third Year Advances Islet
Transplantation
New York City, October 17, 2001 Bolstered by the success of the
Edmonton protocol of 20 patients with type 1 diabetes who received
transplanted insulin-producing islet cells at the University of
Alberta in Edmonton, Canada, 80 percent have achieved independence
from the need for insulin injections for an entire year or more the
prospect of curing diabetes through islet transplantation holds great
promise. JDRF continues to provide strong support for speeding the
transition of islet cell transplantation from lab experiment to human
clinical trials. One institution at the forefront of this field is
the JDRF Center for Islet Transplantation at Harvard Medical School
a $20 million, five-year initiative with a mission to cure diabetes
by islet replacement without the need for long-term use of drugs that
suppress the immune system. It is one of four JDRF Islet
Transplantation Centers, and one of 19 large-scale,
multidisciplinary, high priority JDRF Centers at major institutions
throughout the United States and the world.
The first JDRF Center to be launched (in 1998), the Harvard Center
has just issued its 2000-2001 annual report describing the
accomplishments of its third year. Hugh Auchincloss, Jr., MD, the
Center’s director, summarizes an outstanding year that included
important advances in several areas of islet transplantation,
especially in the use of animal models to induce tolerance in
transplant recipients so they won’t reject implanted islets. And
after months of preparation, clinical trials of islet transplantation
are ready to proceed.
Among the primary accomplishments during the last year:
Monkeys that received islet transplants have survived for more than
100 days even without receiving drugs to suppress the immune system.
Transplantation without immunosuppression is the ultimate goal of the
Center, which holds the position that any procedure requiring
lifelong immune suppression does not constitute a true cure.
A vaccine containing certain immune cells blocked the autoimmune
destruction of islets in non-obese diabetic (NOD) mice, thus
preventing the development of diabetes. If this technique proves to
reverse autoimmune destruction in addition to blocking it, it would
be suitable to apply for support of human clinical trials.
A new laser-based technology allowing dissection on a minuscule scale
enables the Center’s researchers to analyze genetic expression in a
single cell. The material being expressed (messenger RNA) can be
faithfully replicated in amounts large enough to measure expression
of all genes in the cell at the same time. This technology “has
opened an entirely new approach for the investigation of genetic
events in islet regeneration.”
Researchers successfully produced in non-obese diabetic (NOD) mice a
state of “mixed chimerism” the re-education of a transplant
recipient’s immune system to accept donor cells as if they were the
recipient’s own cells. The hope is that the technique of mixed
chimerism can be used to achieve tolerance in humans receiving islet
transplants so that they do not require immunosuppressive drugs.
Changing With the Science
The Center has adapted rapidly as new information about transplants
became available from clinical trials under the Edmonton protocol. As
new research priorities have emerged, the Center has shifted its
focus accordingly. This ongoing review, guided by JDRF’s emphasis on
specific goals and accountability, has had a dramatic effect. “Only
about 50 percent of the Center’s original funding is still allocated
to projects that have the same objectives that they did three years
ago,” Dr. Auchincloss reports. “Furthermore, nine projects are no
longer receiving any funding while 12 completely new projects have
been developed since the first year.”
Clinical Islet Transplants Ready to Proceed
After being selected as one of the sites to be included in the trials
of the JDRF/NIH-sponsored Immune Tolerance Network, the Center
required several months to obtain the equipment and biological
materials necessary to conform exactly to the requirements of the
Edmonton protocol. Dr. Auchincloss reports, “We now have a number of
patients who have had kidney transplants who are now taking the exact
same immunosuppressive drugs as are being used at Edmonton . . .It
should, therefore, be possible to begin clinical islet
transplantation at Harvard this fall.”
Daunting challenges still remain. Immunosuppression, a necessity of
the Edmonton protocol, has harmful long-term consequences.
Researchers still must find a way to overcome autoimmunity so that
the transplanted cells are not attacked by the same immune mechanism
that destroyed the original islets. And perhaps the biggest obstacle
is finding an adequate supply of human islets to make transplantation
widely available. As Dr. Auchincloss pointed out at JDRF’s annual
conference in June, “Using the Edmonton protocol, we have enough
human islets to treat only one-tenth of 1 percent of patients with
Type 1 diabetes.”
The Harvard Center is well-positioned to address these challenges,
however, with a bigger, more vigorous structure than ever before. The
Center’s core services have provided “a remarkable volume of
resources to investigators,” and several young investigators have
been recruited into the Center. “Thus the JDRF Center at Harvard is
helping to train and develop scientists who will pursue diabetes
research in years to come.”
With several new JDRF Centers scheduled to be launched in the months
ahead, we will periodically post reports on all the JDRF Centers.