UPDATES FROM DR. FAUSTMAN’S LAB
AT THE MASSACHUSETTS GENERAL HOSPITAL

Summer 2006
Issue 2For Friends and Supporters: The Diabetes Research and Clinical Trial Program
Dr. Denise Faustman, Massachusetts General Hospital, Building 149, 13th Street, Room 3602, Charlestown, MA 02129

Funding Announcement
We are pleased to announce that the Iacocca
Foundation has generously made its initial grant tothe Massachusetts General Hospital for thepreparation of a human clinical trial to stop theautoimmune attack in type 1 diabetes. The projectwill be divided into three phases: separating T cellsfrom human blood (blood assay), testing in micethe effects of the protocols expected to be used in
the human trial, and the human clinical trial itself.
The current phase of the human studies involves
the sampling of blood from type 1 diabetic
volunteers. The assay will be used for selecting
patients and assessing the efficacy of treating type1 diabetes using BCG.

Thank You!
We are so grateful for the ongoing support frompatients and families. Several fundraising events areplanned for this fall, including:
Bike the Miles for Human Trials on September 10, in
Massachusetts.
Info: Jackie Fusco, 203-249-8238, jefusco@optonline.net
Web: www.bikethemilesforhumantrials.com

Dallas & Reid’s Ride, a motorcycle ride, silent
auction, and field event on September 16, in Indiana.

Thank you to all who have contributed to help make Info: 317-339-7566, info@dallasandreidsride.org
Web: www.dallasandreidsride.org
this work possible.

Answering Your Questions
Why use bacillus Calmette-Guérin (BCG)?
As many of you know, our human clinical trial
program will begin with an evaluation of one limbof the two-limb treatment we successfully used indiabetic mice. We will start with bacillus CalmetteGuérin (BCG), a generic drug with an impeccablehuman safety profile that is currently approved for
two indications—tuberculosis and cancer therapy.
BCG causes the body to make a natural
substance called TNF. TNF helps to regulate theimmune system and can kill a portion of the “bad”
T cells that cause diabetes.
BCG was used many years ago in early-stage
diabetic (NOD) mice and prevented diabetes.
Unfortunately, many compounds work in earlystage NOD mice, but do not work in late-stage
NOD mice or in humans with advanced disease.
BCG was also tried in the past in humans withnew onset diabetes, prior to the knowledge of how
BCG actually works in the body. In the humanstudies, one diabetic patient was cured with asingle dose of BCG, but two subsequent studies
using a single dose of BCG showed no benefit.
We think these early trials of BCG in humans,
although encouraging, could not be advanced until
BCG’s mechanism of action (what it does) wasappreciated and a way to monitor the drug’s effectafter administration was understood. Think about this:If we did not know that insulin regulated blood sugars,
and if we did not know how to measure blood sugar,
how could we measure whether insulin administration
actually worked to help diabetics? In many ways,
early BCG trials are analogous to injecting insulin
without knowing what it really does or how tomeasure its effects. One of our major laboratory
efforts is to have a method for rapidly and preciselycounting the number of ‘bad’ T cells in human bloodand to use this test to evaluate whether BCG caneliminate these cells, and at what dose. -DF

More Good News from Other Labs
Recently, no less than five different groups haveconfirmed our approach to reversing type 1
diabetes, with one group also showing its
applicability to a second autoimmune disease,
Sjogren’s syndrome. I am delighted to see theappearance of these confirmatory studies, now
five years after our original paper. Taken together,
these data provide additional support from thescientific community for the validity of the humanclinical trials we planned with your help. Please
read below for more details.
Positive Results in Sjogren’s Syndrome andDiabetes at the ADA Meeting
Our protocol for eliminating type 1 diabetes inmice has been confirmed and expanded in recentmonths. A group at the National Institutes ofHealth (NIH) led by Tran et al. evaluated theprotocol to see if it would be effective in diabetic
mice that also had Sjogren’s syndrome (Sjogren’ssyndrome is an autoimmune disease affecting themoisture-producing glands, such as the tear andsaliva glands). Excitingly, the researchers foundthat our protocol could be used to reverse twoforms of established autoimmune disease in mice:
type 1 diabetes and Sjogren’s syndrome. Unlike
the papers published in the March 24th issue ofScience, this group found that the spleen did
contribute in part to regeneration of the pancreas
and the salivary glands. The results are submittedfor publication and were presented at the annual
American Diabetes Association’s (ADA) meeting inWashington, DC in June 2006. Data from aJapanese research group, led by Okubo et al. wasalso presented at the ADA meeting and again
confirmed our approach for reversing diabetes inthe type 1 diabetic mouse.
Three JDRF-Funded Labs Show Positive Resultsin Diabetes
On March 24th, many of you saw the articles in theWall Street Journal and New York Times about
our research. On that day, the scientific journal
Science published three papers from threedifferent Juvenile Diabetes Research Foundation(JDRF)-sponsored laboratories (Nishio et al., Suriet al., and Chong et al.) that examined the protocol
our laboratory published in 2001 and 2003 for end
stage diabetes reversal in the NOD mouse. All
three of these studies independently verified, tovarying degrees, that our protocol can "cure" endstage diabetes in mice, that the cure is due to islet
self-rescue or regeneration of the pancreas, andthat it does not require a stem cell or islet celltransplant in the mouse. By cure, we mean that: 1)
the autoimmune attack was sufficiently halted tostop islet destruction and/or promote islet rescue
and regeneration, and 2) the autoimmune diabetes
does not re-occur with long-term follow-up.
In addition to the results described above, the threepapers also reported that the animals had theirdiabetes cured without a role of the splenic stem
cell that we identified in our research. Our original
paper in 2001 and our subsequent paper in 2003
showed that the diabetes cure can be accelerated
by the administration of adult spleen cells in mice.
We also showed that this adult stem cell was not
required, but hastened the speed towards normal
blood sugars. We are still confident that the spleen
plays a role, and the work by Tran et al. at the NIH
also confirms our findings on the spleen. However,this question is not critical to the progress of thePhase I clinical trial. The big picture is thatregeneration was seen and long-term normal blood
sugars were achieved. For a copy of the New YorkTimes and Wall Street Journal articles that covered
this story, please contact:
Jocelyn Hoey
MGH Development Office
165 Cambridge Street, Suite 600
Boston, MA 02114
jhoey@partners.org

Regeneration Panel at the ADA Meeting in June
There was more exciting news at the American
Diabetes Association Meeting this year inWashington, DC. It is, of course, wonderful to“cure” an end stage diabetic mouse using ourtherapy to remove disease and allow the pancreas
Please see Good News continued on page 3“All three of these studies independently verified,to varying degrees, that our protocol can "cure"end stage diabetes mice, that the cure is due toislet self-rescue or regeneration of the pancreas,
and that it does not require a stem cell or islet celltransplant in the mouse.”
Denise Faustman, MD, PhD

Page 3

The Diabetes Research and Clinical Trial Program

Good News (continued from page 2)

Expanding the Research

to regenerate. The next big step is to do the same forhumans with this disease. Although this is the goal of
the MGH program, many groups at this scientificmeeting are reporting that the pancreas of long-term
diabetic patients can show islet proliferation undercertain circumstances. For example, if the Faustman
laboratory hypothesis is correct in the mouse andapplicable to the human, then a human type 1
diabetic with a pancreas or islet transplant who istaking high dose immunosuppressive drugs could
possibly start to see the regeneration of islets in hisor her own pancreas. Indeed, the blood sampling oflong-term diabetics is showing that, in some cases
after pancreas or islet transplantation, the insulin canoriginate from the patient’s own pancreas. Althoughhigh dose immunosuppressive drugs are toxic
treatment and probably also diminish islet
proliferation, this human data suggests that evenafter longstanding and established disease, thepancreas is still trying to regenerate. If the humanpancreas has the natural ability to regenerate indiabetes, but the disease burden prevents effective
islet regeneration and survival, the idea of disease
removal remains stronger than ever as a majorclinical goal.

Our clinical trial led by Dr. David Nathan will soontest the generic drug bacillus Calmette-Guérin(BCG) to see if it can specifically eliminate thedisease-causing T cells in type 1 diabetic patients.
Although we hope that the BCG will have abeneficial effect in type 1 diabetes, we also believethat permanently eliminating the disease will
require “re-training” the immune system so that it
does not attack the body’s own cells. We recentlyreceived preliminary funding from Friends Unitedfor Juvenile Diabetes Research that will enable us
to begin looking for other inexpensive, non-toxic
compounds in the lab that might be of benefit in ourdiabetes work. We hope to begin screening for
generic drugs that can be used as new treatments
not only for type 1 diabetes, but also for otherautoimmune diseases, including lupus, rheumatoid
arthritis, scleroderma, multiple sclerosis andSjogren’s disease. We are actively raising funds forthis research. We are sending out grant requests
regularly to start on our project to screen existing
generic drug candidates for uses in various
autoimmune diseases — type 1 diabetes, lupus,
rheumatoid arthritis, scleroderma, multiple sclerosis
and Sjogren’s disease.

EventsI was invited to give several talks this spring focusing on the regeneration of islets in type 1 diabetes. At BIO,
the world’s largest biotechnology meeting, I organized a symposium on “Regenerative Therapies, from Benchto Bedside.” I also had the pleasure of organizing an American Association for the Advancement of Science
symposium on new autoimmune therapies. A major theme of this symposium was the concept that new
autoimmune diseases induced by currently approved anti-TNF drugs are the same human autoimmune
diseases in which patients would instead benefit from therapies that induce, rather than suppress, TNF. I alsopresented our data in Rome at the International Symposium on “Prevention of Type 1 Diabetes: The NewFrontier.” I continue to be encouraged that other scientists and labs are taking interest in our research.

“One of our major laboratory efforts is to have amethod for rapidly and precisely counting thenumber of ‘bad’ T cells in human blood and to use
this test to evaluate whether BCG can eliminate
these cells, and at what dose.”
Denise Faustman, MD, PhD

Please Support Our Research to Find a Cure
Please support the ongoing research of our lab with your tax-deductible donation. Donations may bemade by check (payable to “Massachusetts General Hospital”) and can be sent to:
Jocelyn Hoey
MGH Development Office
165 Cambridge Street, Suite 600
Boston, MA 02114
Please indicate: “Type 1 diabetes research” or “Autoimmune research” on memo line
To make a secure online donation, please visit: www.mgh.harvard.edu/diabetes/diabetes_support.htm. Clickon “Type 1 Research.”
For clinical trial enrollment or to enroll in the current blood testing for the trial, please email or contact:
Lynne Murphy
Assistant to Dr. Denise Faustman
Immunobiology Laboratory
Building 149, 13th Street, CNY-3601
Charlestown, MA 02129
617-726-4084
DiabetesTrial@partners.org

Web updates are available at: www.mgh.harvard.edu/diabetes