Updates

from the Faustman Laboratory at Massachusetts General Hospital

Fall 2023

A Note from Dr. Faustman
The Phase II BCG clinical trial
in adults with longstanding
type 1 diabetes is nearing
completion. There is still a lotof work to be done analyzing
the data and preparing for
publication. This Phase II
BCG trial is the first large,
placebo-controlled trial
of BCG as a treatment forestablished type 1 diabetes,
and the read-out is a major
milestone for our lab andeveryone impacted by type 1 who might be eligible todiabetes. Stay tuned!
contact the lab.
We have not, however,forgotten the children.
We currently have two new
BCG pediatric trials that areopen and actively recruiting,including the most recent
trial in “new-onset” children.
Please encourage anyone

BCG is a safe and affordable
vaccine, but these
FDA-regulated trials are
expensive to run. We havecome this far through thesupport of patients andfamilies impacted by type 1
diabetes. We hope you

will help us move thisimportant work forward.
Please contact us if you
have any questions,diabetestrial@partners.org.
Sincerely,

Denise L. Faustman, MD, PhD

UpdateFall 2023

BCG Clinical Trials to Reverse Type 1 Diabetes
More than 500 individuals with type 1 diabetes have been enrolled or are scheduled to enroll in ongoing
BCG clinical trials at MGH. This includes almost 300 type 1 diabetic subjects who have been treated with BCG.

Adult Clinical Trials

Pediatric Clinical Trials

The adult Phase II BCG trial is almost complete. All 150
patients have been followed for at least five years. The
trial has two groups: BCG (100 patients) vs placebo (50patients). The primary outcome of the trial is HbA1c,
which is the clinical measurement of blood sugar control
and the most impactful biomarker of type 1 diabetes.
Several important secondary outcomes being followed
include insulin use and c-peptide, the measurement ofendogenous insulin production.

Type 1 diabetes is often called juvenile-onset diabetes
because the majority of people with type 1 diabetes arediagnosed as children. When the adult Phase II trial was
fully enrolled, we applied to the FDA to start pediatrictrials. In 2022, we launched the first trial in children
ages 12 to 18 who have lived with type 1 diabetes forat least two years. This year, we launched a second
pediatric trial in children ages 8 to 18 who have had
type 1 diabetes for less than a year.

When all of the patients in the trial have reached their
Please contact the lab if you or someone you know
five-year follow up, the next steps will be data analysis and would like to learn more about participating!
ultimately peer review publication. This process can takea year. Plans for a Phase III trial are already underway.

Research Updates
While the clinical trials advanced, we continued ourefforts to understand the underlying mechanismsof BCG and type 1 diabetes. This included newpublications, as well as presentations at the Endocrine
Society, Federation of Clinical Immunology Societies,
and the Immunology of Diabetes Society. Topics ranged
from prevention of type 1 diabetes to immune systemchanges in type 1 diabetes driven by BCG.
Infections: Current Clinical Trial
Cumulative Infections per Patient

0.5

BCG
Pbo

0.4
0.3
0.2
0.1
0.0

0.0

0.5

1.0

1.5

Years since 1/1/2020

Infections: Before and During Current Trial
0.6

BCGInfections per Patient✱✱
0.4

0.2

0.0
Pretrial (~30 months)

Current Trial (15 months)

Placebo

Not long after BCG was introduced 100years ago, the evidence began to come inthat BCG could protect against a range
of infections beyond tuberculosis. Albert
Calmette, BCG’s co-inventor, noted a 4-folddecline in child mortality (unrelatedto tuberculosis) in vaccinated children.
During the COVID-19 pandemic, we
looked at BCG and infectious disease.
Our lab published data showing that BCG
protects against a broad range of infectiousdisease symptoms from bacterial and viral
infections.

www.faustmanlab.org

BCG Working Group

About BCG

Viviane Callier from Scientific American attended
our October 2022 BCG Working Group conference. Theresult was a terrific summary of both the meeting and theexplosion of global research on the “off target” effects ofBCG. The article, published in March, is available on theScientific American web site.

BCG is a live, attenuated bacterial
vaccine derived from Mycobacterium
bovis. Discovered over 100 years ago atthe Pasteur Institute in Paris, BCG has
historically been given to protect againsttuberculosis. In the history of medicine it
is considered to be extremely safe, is on theWorld Health Organization’s Model List ofEssential Medicines for adults and children,and is given to roughly 100 million children
per year globally. Over the last twentyyears, a growing group of researchers andclinicians have begun to explore the “offtarget” effects of BCG for diseases including
type 1 diabetes, multiple sclerosis, allergy,
fibromyalgia, Alzheimer’s disease andrespiratory infections such as COVID-19.

In 2024, we will be convening the 6th International BCGWorking Group. Each year, the group grows bigger and thedata gets more compelling. In 2022, we had researchers
from around the globe join us, stretching from Stanford to
the University of Melbourne in Australia.

Three Questions for Dr. Faustman

BCG Beyond Type 1: Alzheimer’s,
Infectious Disease and More
In 2023, a neurology group we collaborate with at MGH
published new data on Alzheimer’s disease and BCG in
JAMA Open Network. The BCG-treated patients had a lower
rate of Alzheimer’s disease and related dementias with aneven lower rate among patients age 70 years or older at thetime of treatment. Alzheimer’s disease is also a complicationof type 1 diabetes.
“Our team, consisting of several uro-oncologists as well
as Alzheimer’s disease researchers, was surprised andexcited to see the striking association of BCG treatment
with lower mortality in Alzheimer’s disease,” said Marc S.
Weinberg, MD, PhD, principal investigator and physician
in the Alzheimer’s clinical and translational research
unit at Massachusetts General Hospital. “This was not
the primary goal of the study but may suggest that BCG
should be studied for potential benefits to mortality
outside of the context of neurologic disease.”(Source: Helio)

Is BCG immunosuppressive?
No. BCG works in long-term diabetic subjects bycorrecting an underlying defect in the white bloodcells. The BCG vaccine gradually re-teaches the whitebloods to correctly utilize sugar, not fats, for energy.
This regulated blood sugar transport lowers HbA1cvalues long term. In the trials in children, we hopeto additionally see if BCG will work to halt the whiteblood cells from attacking the insulin-producing cells.
Why is age of onset important in type 1 diabetes?
Age of onset refers to the age a person was when they
were diagnosed with type 1 diabetes. It is importantbecause it helps us characterize patients and may
predict response. We know that those who werediagnosed as children are more responsive to BCG
than patients diagnosed as adults, regardless of age
at treatment, since the early age of onset means avery aggressive immune response to self.
Could BCG be used to prevent type 1 diabetes?
We are not conducting prevention trials, but there isevidence that multiple doses of BCG could preventor delay the onset of type 1 diabetes. For example,
researchers in Turkey and Greece have looked atrecords of BCG vaccination and found that theincidence of type 1 diabetes was significantly higher
in children who did not have two or more BCG shots.
It would certainly be interesting to conduct a large,
placebo-controlled prevention trial at some point.

UpdateFall 2023

FUNDRAISINGHow You Can Help

Want to Host an Event?
If you are interested in hosting an event, please contact the lab
directly. MGH has a terrific community fundraising tool called
BeCause. For the last 20 years, community fundraisers like bikerides and dance parties have created a big impact on the awareness and funding of our research. Lee Iacocca used to say about
the BCG trials, “These trials are for the people and by the people.”
Get inspired and keep inspiring us. Please contact the lab formore information.

Donor Spotlight:
Friends United for Juvenile
Diabetes Research
In 1999, Susan Mandell founded
Friends United for Juvenile Diabetes
Research. We recently caught up
with our “Friends” Susan and her
co-president Carol Emer about their
Chicago-based philanthropy.

What was the inspiration for Friends United?
We are both personally impacted by type 1 diabetes. I (Carol) have
had type 1 for 43 years. Susan’s son Josh was diagnosed with type
1 at the age of 8. He is now 35. We had been fundraising for theJDRF, but we wanted to do something to move research forward
directly without any middlemen. We wanted to know that 100% ofwhat we raised was going to the research we were interested in.
How did you find out about BCG?
My (Carol’s) father read an article about Denise’s research and
we reached out to her to learn more. From day one, she wasso generous with her time. She even attended some of ourChicago events.

Please consider making atax-deductible donation to thistype 1 diabetes research program.
Every gift makes a difference.
1. To make a secure online donation,
visit www.faustmanlab.org andclick on “Donate.”
2. You may make a gift by check(payable to “Massachusetts
General Hospital”) and mailit to:
Diabetes Clinical Trial
c/o Dr. Denise Faustman
Immunobiology Laboratory
MGH - EastBuilding 149, 13th Street, CNY-3601
Charlestown, MA 02129

On the memo line, please write:“Faustman T1D research.”Thank you for joining us in thefight against diabetes!

Tell us a little bit about the events you held?
We did big “gala” type events with food and entertainment.
Those were great fun, but also a lot of work and expense.
They took a big team, but the results were fantastic. Some ofour smaller initiatives like game nights were very productive
as well. We tried to make everything fun.

For more information, visit
www.faustmanlab.org or email
DiabetesTrial@partners.org.

When you started, did you think you would end up raising as
much as you did?
No, we certainly did not think we would be raising more thana million dollars over the run of our efforts, but it was a nicesurprise. It is amazing to see some of that research, especially theBCG clinical trials, move from the “idea” stage into clinical trials.

Follow us on X (Twitter):
www.twitter.com/FaustmanLab

Any advice to families looking to get involved?
Keep it simple. None of us ever took salaries, so everything weraised except for the event costs went right to research. Keepcosts low and pick research projects you are excited about.

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

Follow us on Instagram:
www.instagram.com/FaustmanLab