Updates
Fall 2013

from the Faustman Laboratory at Massachusetts General Hospital

A Note from Dr. FaustmanI

hope everyone has enjoyed thesummer! As we enter the fall,
we are looking forward to seeing
many of you who are scheduled
for blood donations at the laboratory. We are also moving closer
to participant enrollment for thePhase II clinical trial of BCG in
long-term diabetics.
Several things still need to bedone before we get to that point.
One of the most important steps
is completing ongoing researchin our laboratory that will give us
information about how to design
the trial -- specifically, how todefine subgroups among longterm diabetics.
A clinical trial subgroup is agroup of subjects that all have asimilar characteristic. We want tolook at that characteristic—suchas “less than 10 years living withdiabetes”—to see if it influences
how participants who havethe characteristic respond totreatment compared to others.

Using this example, we might
examine how “subjects livingwith diabetes for less than 10years” (subgroup 1) compare to“subjects with 10 or more years ofdiabetes” (subgroup 2).
In the upcoming Phase II
clinical study, we would liketo see if there are any trends
among people with different
durations of type 1 diabetes
and different rates of C-peptide
decay (the protein that is amarker of insulin secretion fromthe pancreas). Therefore, inthe laboratory, we are currently
looking at how rates of C-peptide
decay and biological variation in
C-peptide secretion might differ
in individual participants, as wellas in subgroups of participants
who had the same age ofdiabetes onset. This is extremely
important because it will allow usto define the overall number ofstudy groups for the Phase II trial,in addition to the size of thesevarious groups and the durationthat we should study eachsubgroup.
We are also excited to be
conducting follow-up studiesof participants from the Phase
I trial who received BCG
vaccinations to identify any
long-term effects. I hope toprovide you an update on thatdata in the coming months.
Thank you all for yourcontinued support!
Sincerely,

Denise L. Faustman, MD, PhD

UpdateFall 2013

Meeting in London to Bring
Together Experts on BCG, TNF andAutoimmunity
Dr. Faustman has planned a meeting this Octoberthat will bring together researchers from around theworld who are investigating the effects of BCG in
autoimmunity and the TNF pathway in autoimmune
diseases. (BCG is the inexpensive generic drug
we are using in our type 1 diabetes trials to help
recipients boost production of their bodies’ TNF,
since we think TNF is beneficial for eliminating thealtered immune response in type 1 diabetes, andprobably other autoimmune diseases).
This is the first time these international
researchers will meet to share backgroundand updates on animal data, human data andbest practices across different geographies andautoimmune conditions. They will discuss thefuture of BCG and TNF in autoimmune disorders
such as type 1 diabetes, multiple sclerosis, Sjögren’s
syndrome and celiac disease, as well as how
collaboration could benefit ongoing research andsubjects affected by these diseases. The meeting,“BCG and TNF Signalling in the Treatment andPrevention of Autoimmune Diseases – 2013,” isbeing philanthropically sponsored and will takeplace in London. A book based on the meeting willbe published by the scientific publisher Elsevier.

Approaching Our Goal
We now have nearly $17.2 million raised for thePhase II clinical trial.
We are pushing to meet our goal of $25.2
million by the end of 2014.
Thank you to everyone who has helped
us get where we are today, and to all of those who
are working hard to help us reach this goal!
For information on how you can help support
this research, please see the back page,“How You Can Help.”

Confirmatory Data at the ADA
Meeting
In 2012, the Faustman Laboratory’s paper,“Persistence of Prolonged C-peptide Production in
Type 1 Diabetes as Measured with an Ultrasensitive
C-peptide Assay,” was published in Diabetes Care.
In it, we shared our data showing that the declineof insulin-production (measured with C-peptide)occurs much more slowly than scientists havetraditionally thought. Using an ultrasensitive blood
test, we found that C-peptide production can persist
for decades after type 1 diabetes onset and remain
responsive to blood sugar levels. Indeed, C-peptide
was detected in 10% of patients in our study who
had been living with the disease for 31-40 years.
This year, we were excited to see data presented
at the American Diabetes Association’s scientificmeeting that further confirm our findings. “TheMajority of Patients with Over 5 Years of Type 1
Diabetes Are Insulin Microsecretors and Have
Functioning Beta-Cells” (Poster 1836-P) was sharedby a team from the UK, who also found enduring,
low-level insulin production in the majorityof patients with type 1 diabetes. This was also
confirmed by a multicenter study performed in theU.S. (“Residual C-Peptide in Patients 3-81 Yearsfrom Diagnosis of T1D: A T1D Exchange Study,”
Poster 1616-P).
Together, these findings are good news forpeople who have been living with diabetes for manyyears, showing that they may have the chance torecover insulin secretion. Overall, there may be alonger period in which we may be able to intervene
in type 1 diabetes, for instance, by stopping thedisease from progressing or by regenerating theinsulin-producing cells to reverse the disease—even in people who have been living with thedisease for decades.

www.faustmanlab.org

Stephen Schwartz Hosts Evening for MGH
Diabetes on Broadway
On June 11th, musical theater lyricist and composer
Stephen Schwartz hosted a private dinner for 100 type1 diabetes advocates and donors to the Faustman
Laboratory at Massachusetts General Hospital. Thedinner was at legendary theater district restaurant Sardi’sin New York City. Guests followed Stephen to the MusicBox Theater for a performance of his multiple Tonyaward-winning show, Pippin. After the show, guests
enjoyed cocktails with the cast. Funds raised by theevent went to support the Faustman Laboratory’s type 1
diabetes program at Massachusetts General Hospital.
Guests included (and pictured right): Ben Vereen (Tony Winner forthe original Pippin and Roots star), Dr. Denise Faustman (Harvard/MGH), Stephen Schwartz (Composer of Music and Lyrics for
Pippin, Godspell and Wicked) and Megan Hilty (Wicked, Smash).

Frequently Asked Questions
Am I currently registered for potential participation in the trial or registered to be informed of updates?

Please email diabetestrial@partners.org with your name, updated mailing address, phone number, andemail. We find that people’s contact information changes frequently; by emailing us you can ensure you arein our database. The clinical trial coordinators will email you back to confirm that you are registered in ourdatabase or will send you the forms to register if this has not yet happened.
What are you doing right now to prepare for the Phase II trial?

We currently have clinical research in progress that is looking at long-term diabetics who have various
durations of type 1 diabetes and various ages of onset. In these participants, we are seeking to define precisely
the rates of C-peptide decay over decades and the biological variation in C-peptide secretion in the same
participant followed over time. This is extremely important because it will allow us to define the overall
number of study groups (based on homogeneous characteristics related to rate of C-peptide decline, age ofonset, etc.), the size of various Phase II study groups, and the duration we will study each of these groups.
We are currently screening subjects every day in the laboratory to look at these specific immune
system parameters and remaining pancreas function in preparation for the Phase II study. Please email
diabetestrial@partners.org or call 617-726-4084 if you wish to make an appointment.
How will candidates be chosen to participate in the Phase II trial?

Participant eligibility will be decided in consultation with our clinical advisors and the FDA. We ask
interested parties to register their information or schedule to come for a visit us so we can do detailed T cellwork on your blood. This will help us formulate study groups when we launch the trial. For more information
on how to participate, please email us at diabetestrial@partners.org.

UpdateFall 2013About the Type 1 Diabetes Reversal
Trials at MGH
Led by Dr. Denise Faustman at Massachusetts General
Hospital (MGH), the BCG Human Clinical Trial Programis testing Bacillus Calmette-Guérin (BCG), an inexpensive
generic drug, as a treatment for advanced type 1 diabetes. Inthe Phase I human study, BCG was administered to adults who
had been living with type 1 diabetes for an average of 15 years.
This treatment not only helped eliminate the defective T cells
that mistakenly attack and destroy the insulin-producing cellsof the pancreas, it also temporarily restored the ability of thepancreas to produce small amounts of insulin. The next step,a Phase II study, is currently being planned, with the goal ofidentifying the drug dose and schedule that will put advanced
type 1 diabetes into remission.

Our Inspiration

How You Can Help
Please consider making a taxdeductible donation today tosustain the momentum of this type1 diabetes research program. Every
gift makes a difference for patients… today and tomorrow.
1. To make a secure online
donation, please visit
www.faustmanlab.org andclick on “Support.”
2. You may make a gift by check(**payable to “Massachusetts
General Hospital”**) and mailyour check to:
Diabetes Clinical Trial
c/o Dr. Denise Faustman
Immunobiology Laboratory
Massachusetts General
Hospital-East
Building 149, 13th Street, CNY-3601
Charlestown, MA 02129

On the memo line of your check,please write: “Type 1 diabetesresearch.”Thanks to all of our participants and supporters of this research! Do you haveany pictures you’d like us to have? Email or send them in and we will post
them on our visit board. We would love to have them!

Thank you for joining us in thefight against diabetes!

Looking for more information about this type 1 diabetes research?
Please visit www.faustmanlab.org.

Find us on Facebook:www.facebook.com/FaustmanLab

Have questions about participating in future studies?
Please email: DiabetesTrial@partners.org.

Follow us on Twitter:
www.twitter.com/FaustmanLab