Updates
Fall/Winter 2008

from the Faustman Laboratory at Massachusetts General Hospital

Major
Advancement
in Potential New Therapy
for Type 1 Diabetes

We are in the midst of
our Phase I clinical
trial evaluating the effectsof Bacillus Calmette-Guérin(BCG) in type 1 diabetes. The
trial is being conducted here
at Massachusetts GeneralHospital. Our lab recently
completed an exciting study
that confirms the mechanism
behind BCG, our potential
new therapy.
The study, published in theSeptember 9, 2008 issue of theProceedings of the National
Academy of Sciences, wasconducted using human cells.
It showed that activating ametabolic pathway that helps
regulate the immune system

specifically eliminates thedefective T cells (a type of whiteblood cell) that react against apatient’s own tissues.
Previously, we had discovereda technique that reversed type1 diabetes in mice, which has
been the basis of our current
Phase I human clinical trial.
Our mouse studies showed
we could selectively kill thedefective T cells that weredestroying insulin-producing
islet cells of the pancreas.
Our latest study is the first

We’re launching a new web site
The Faustman Lab web site has undergone amajor redesign and includes expanded information.
Visit the site today at www.faustmanlab.org andlearn more about the trials and how you cansupport them. You can also sign up for
e-mail updates.

demonstration that thisstrategy also works in humancells and supports the viabilityof the clinical trial that iscurrently underway.
In previous studies, our teamdemonstrated that causing
diabetic mice to produce
elevated levels of tumor
necrosis factor (a substanceproduced by the body thathelps to regulate the immunesystem) leads to the death ofthe defective T cells responsible
for the destruction of healthy
islet cells (cells in the pancreasthat produce insulin). After thedefective T cells were destroyed
and the immune systembecame devoid of defectivecells, the mice were able toregenerate healthy islet cells
that produced normal levels
of insulin. In other words,
the animals were cured of
their disease.

Fall/Winter 2008

New Way to Kill Defective Cells
Spares Healthy OnesO

ur most recent study
used blood samples from
more than 1,000 people withautoimmunity compared tomatched volunteers withoutautoimmunity.
First, we found in tissue culture
experiments the treatment withtumor necrosis factor, or TNF,
killed the defective T cells foundin the blood of patients with type1 diabetes and other autoimmune
diseases, but did not have any
effect on the healthy cells of thecontrol patients. This is a goodoutcome because we want todestroy only the defective cells,
and not the healthy ones. Then
we tested several substances,called TNF agonists, that produce
an effect in the body similar tothat of TNF. We found that oneof these substances was
also effective in destroying
the defective T cells in thetissue culture of diabetic andautoimmune patients, whilesparing healthy cells. Further
experiments with the blood
samples of diabetic patients
confirmed that our treatment
only leads to the death of thedefective T cells responsible
for producing an autoimmune
reaction (the attack of the islet
cells of the pancreas) in thesepatients, and does not harm
healthy cells.

These findings are importantbecause they provide further
evidence — and the first in
human T cells in culture — that
our approach in the current
human clinical trial does notappear to harm healthy cells
and appears to kill in culture thedisease-causing cells.
The current Phase I trial began
in January, 2008. In it, a genericdrug is being tested in patientswith type 1 diabetes to determine
whether the drug will cause thedeath of the defective T cells that
destroy the pancreatic islet cells.
For more information, see“Update on the Clinical Trial.”

Image used for illustrative purposes

Updateswww.faustmanlab.org

Update on the Clinical TrialOur human clinical trial
is testing whether using
Bacillus Calmette-Guérin(BCG), a generic drug that
temporarily elevates TNF levelsin the body, will reduce oreliminate autoimmune T cells
in patients with type 1 diabetes.
The trial’s Phase I funding iscomplete and the trial is inprogress under the directionof Denise Faustman, MD,PhD, and David Nathan, MD,
director of the MGH Diabetes
Center.
The trial, scheduled forcompletion by January, 2010,

will gather information on drug
safety. Subsequent Phase II
trials will focus on determining
the optimal dose and timingof BCG administration toachieve the desired effects intype 1 diabetes. Phase I trials
are aimed at proving the drugis safe.
While this trial is underway,
we need to begin planning for
our Phase II clinical trial, which
we hope to launch upon thesuccessful completion of thePhase I portion. The Phase II
trial will involve testing BCG
in greater numbers of patientswith type 1 diabetes using thedose and timing we determine
from the Phase I data. It will
also give us more information
on how effective this treatment
might be, providing theinformation needed to launchlate-stage human clinical trials(Phase III studies). We are
currently screening volunteers
for the Phase II trial.
A major part of the Phase IIplanning involves raising thefunds needed to conduct thisnext stage of human research,
and we have set a fund-raisinggoal of $25 million.

In the Media

Denise Faustman, MD, PhD,on Talk of the Nation’s “Science Friday”
In September, Dr. Faustman had the privilege of joining radio
host Ira Flatow on National Public Radio’s Talk of the Nation. The“Science Friday” segment discussed many aspects of diabetes, ourresearch and our current clinical trial. Here are some highlightsfrom our conversation that address some aspects of the work being
done at the Immunobiology Lab. For a full transcript, please visit
www.faustmanlab.org.
Regarding our approach to eliminating thedisease-causing cells in type 1 diabetes:
FLATOW: And how do you go about killingthese bad white blood cells?
DR. FAUSTMAN: Oh, that’s kind of the fun partof this project, because we’re using a vaccine
that’s been out there for about 80 years, andthe vaccine’s called BCG. In the rest of the world,
outside of the United States, it’s a mandatory
vaccine … to prevent tuberculosis (TB).
In the U.S., it’s used for cancer. And the reason
we’re interested in that vaccine is that it induces

something in your body called TNF, tumor
necrosis factor. We think the way to kill one
population of these rogue T cells, whether you’rea mouse or whether you’re human, is with TNF.
FLATOW: And so you’re trying that out inhumans now?
DR. FAUSTMAN: Yes … we’re actually in humanclinical trials. We’re not sure if the humans aregoing to be as happy as the mice;
we’re very early in the process oftesting it. But the Phase 1 trials
are ongoing here in Boston.

Updates

Fall/Winter 2008

Two Ways
You Can Help
Please support theongoing research of ourlab with a tax-deductible
donation. Every gift makesa difference for patients …
today and tomorrow.
1. To make a secure online
donation, please visit
www.faustmanlab.org
and click on “Support.”

Fund Raising:
Creative Ways to Get Involved

In the spring of 2008, theBallet Foundation for theXXI Century dedicated its
Dance Festival to one ofthe Foundation’s students,
Madeleine Howells. Madeleine
was diagnosed with diabetes
while in the second grade,but never let the challenge
get in the way of her passion
for dance. Now, at age 13,
Madeleine not only keeps up
with ballet, but also excels inher class.
For the Foundation’s Dance
Festival 2008, a lyrical piece
was choreographed to feature
Madeleine. The piece, entitled“World,” was arranged by thecompany’s prima ballerina,
Leia Hardimon, and set tothe music of artist Five forFighting.
The Ballet Foundation
generously collecteddonations during the festival
to benefit Massachusetts
General Hospital’s type 1
diabetes research, and thedonations totaled more than
$1,400. We greatly admire
Madeleine for pursuing her
passion in spite of having thischallenging disease and wewould like to thank everyone
who was kind enough to makea donation in support of ourresearch efforts.

2. You may make a giftby check (payable to“Massachusetts GeneralHospital”) and mail yourcheck to:
MGH Development Office
Attn: Jocelyn Hoey
165 Cambridge Street
Suite 600
Boston, MA 02114
On the memo line of yourcheck, please write: “Type1 diabetes research” or“Autoimmune research.”Thank you for joining us in
the fight against diabetes.
Warmly,Denise L. Faustman,
MD, PhD