Updates

from the Faustman Laboratory at Massachusetts General Hospital

Fall 2021

A Note from Dr. Faustman
As you can imagine, 2021

certainly kept us on our toes.
The pandemic came, went andcame back again. Despite it all,the lab kept going and patientsin the diabetes trials came for
their trial appointments. We
continue to follow the patientsin the Phase II trials. We arealso prepared to launch thepediatric trial we have fought
so long to start. Not including
the pediatric trial, we arenearing 250 trial participants
enrolled, of which 143 havereceived at least two dosesof BCG.
Clinical trials are long andThe data supporting BCG
continues to grow. The Annual expensive journeys, but the
reward is worth the effort.
Scientific Sessions of theAmerican Diabetes Association A safe and affordable
intervention like BCG has
were virtual this year, but ourpresentation was well received the potential to fundamentally
alter how we treat and pay
and highlighted important
for type 1 diabetes.
new data on the role age of
onset plays in BCG therapy
The need for a treatment thatand how BCG alters theregulatory cells in the immune reverses established type 1
diabetes has never been greater.
system in type 1 diabetes.

The prevalence and economic
burden are growing each year.
We hope you will help us
move this important workforward. Please contact uswith any questions,diabetestrial@partners.org.
Sincerely,

Denise L. Faustman, MD, PhD

UpdateFall 2021

New Data in 2021
In 2021, we published and presented new data that
• Glucose metabolic effects of BCG in diabetes
helps increase our understanding of how BCG changes
BCG vaccinations improve glycemic control inglucose metabolism and interacts with the immune
juvenile-onset type 1 diabetes (T1D), an effectsystem. These results include new data on open label
driven, in part, by restored sugar transport in thepatients that have been followed for several years andwhite blood cells of diabetic people. In a pilot
expands on the results from the Phase 1 trial.
clinical trial, patients with T1D, but not latentautoimmune diabetes of adults (LADA), exhibited• BCG therapy is associated with long-term, durable
lower blood sugars after multi-dose BCG. Using
induction of Treg signature genes by desirable
a glucose transport assay, white blood cells fromgene modulations
T1D subjects showed improved sugar transport
Multi-dose BCG vaccinations result in systemic longwith BCG exposures; LADA subjects showedterm induction of T cells that help to quiet the immunesystem, the Treg cells. In type 1 diabetes, less potent Treg minimal BCG-induced sugar responsiveness.
cells contribute to the underlying autoimmune disease. • Gene changes related to glucose metabolism
The clinical time course of BCG-related improvements
in type 1 diabetes after BCG vaccinations:(2–3 years post-vaccination) correlates with the slow
A vital role for KDM2B - Why is BCG so powerfulTreg induction through gene changes. This was manifest
in diabetes management?
by a general pattern of turning on key signature genes
Restored glucose transport with BCG is regulatedof an immunosuppressive Treg cell. In autoimmunity,
by genes. This new study identified two genes
this represents a restoration of Treg biology to near(KDM2B and DDIT4) as genes controlling BCGnormal expression levels thus demonstrating BCGdriven facilitated and restored glucose transport,
microorganism synergy and a relatively simple albeit
respectively. The BCG effect at the gene level wasslow and steady approach to the restoration of Treg
confirmed by looking for both improved/restored
function in humans.
proteins and white blood cell function.

Updates at the ADA
The 2021 American
Diabetes Association
meeting was virtual, but
the lab was able to present
several key updates
including new data on how
BCG treatment restoresFoxp3 genes, associated withregulatory T cells (Tregs),
towards normal DNA
patterns. Poor Tregs havebeen identified as playing a
key role in the progressionof type 1 diabetes.

www.faustmanlab.org

Type 1 Diabetes Clinical Trials

About BCG

The Phase II trial continues to progress. All 150
patients have been followed for more than three years.
The trial will not read out until the last patient enrolled
reaches five years of follow up, but the lab is not just
waiting around. The Phase II trial is one of several
ongoing studies in the lab, including a soon-to-belaunched multi-center pediatric trial. At the end of thePhase II trial, all of the patients will have been followed
for five years for key biomarkers of type 1 diabetes
including HbA1c, c-peptide and insulin use.

BCG is a live, attenuated bacterial
vaccine derived from Mycobacterium
bovis. Discovered over 100 years ago
at the Pasteur Institute in Paris, BCG
has historically been given to protect
against tuberculosis and in the historyof medicine is considered to be
extremely safe, is on the World HealthOrganization’s Model List of Essential
Medicines for adults and children, andis given to roughly 100 million children
per year globally. Over the last twentyyears, a growing group of researchersand clinicians have begun to explore
the effects of BCG for diseases
including type 1 diabetes, multiple
sclerosis, allergy, fibromyalgia,Alzheimer’s and respiratory infections
such as COVID-19. 2021 is the 100thanniversary of the first administrationof BCG. In commemoration, theInstitute Pasteur de Lille is organizing
an international BCG conference.
Dr. Faustman has been invited to speak
about BCG and type 1 diabetes.

Early next year we will be starting a 150 patient multicenter pediatric trial in adolescents with diabetes.
The timing could not be more pressing. A study in
the American Journal of Managed Care published in
September 2021 found the estimated T1D prevalenceper 1000 youths aged 19 or younger increased by 45%
over the last 16 years.

Teddy Talks

The Economics of Type 1 Diabetes.
For many living with type 1 diabetes, the healthimpact is compounded by an enormous financial
burden. Insulin remains an expensive drug and, formany uninsured, insulin rationing is a dangerous
reality. Based on data from a large non-profit healthplan, the average medical expenditures for a personwith type 1 diabetes are roughly $22,000/year($13,000 medical and $9,000 pharmacy) of which$14,500 can be attributed to type 1 diabetes.

As we initiate pediatric trials, we arethrilled to partner with award-winningchildren’s book author Vanessa Messenger
on her new book, Teddy Talks: A Pawsitive Story About Type 1 Diabetes, whichshowcases type 1 diabetes through theeyes of a loved one by explaining thecondition and management through acontinuous glucose monitoring device ina fun and digestibleway. A portion ofproceeds from thesale of this bookwill benefit theBCG clinical trials
at MGH.

UpdateFall 2021

FUNDRAISINGHow You Can Help

Events come back
COVID-19 changed where many events were held, but that did notstop inspired donors from organizing golf tournaments, mountainclimbs and other events. We hope 2022 will have even more. If you
are interested in hosting an event, please contact the lab directly.

Please consider making a
tax-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.”

The “Kiss the Sky” on the Pacific Crest Trail

Donor Spotlight, The Noble family
The Noble family has been one of the Lab’s most ardent supporters.
They recently told us a little of their story:

2. You may make a gift by check(payable to “Massachusetts
General Hospital”) and mailit to:
Diabetes Clinical Trial
c/o Dr. Denise Faustman

Why is your family climbing for a cure?

Immunobiology Laboratory

Our daughter Kate was just 16 months old when we learned that she had
T1D. The doctors told us there was “no cure.” That was January 2, 1992.
Ten years later, driving past the High Sierra, I said I wanted to climb MountWhitney and Kate suggested: “Why don’t you do a hike-a-thon for diabetes?”
We launched Kiss the Sky to Conquer Diabetes with a simple thought:“Keep climbing until we Conquer Diabetes!” That summer, I reached thesummit of Mount Whitney.

MGH - East

How long have you been supporting the lab? How did you get started?
In 2004, KTS teamed up with The Iacocca Foundation’s Join Lee Now
initiative and have been climbing to support Dr. Faustman and her team’s
efforts to find a cure for diabetes ever since. The KTS teams have hiked
hundreds of miles and reached the summits of dozens of peaks, including
Mount Shasta and Mount Hood, and climbed in the Cordillera Real in Bolivia
to raise funds to support clinical trials of BCG.

Building 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!

Can you tell us about the 2021 climb?
Nathan (who I met on the Rainier climb in 2004 and who has joined meon almost every KTS climb since) wanted for 2019 to do a “thru hike.” So, in2019, we had planned to do the 72 mile High Sierra Trail, but we got snowedout. We tried again in 2020, but COVID closed it. In 2021, we were trained,packed and ready to go when we were delayed by a COVID exposure. So,
we changed plans while we waited and got permits to instead hike 50 miles
along on the Pacific Crest Trail and John Muir Trail. We did have severethunderstorms each afternoon and ended up revising plans again to push
more each day, but the journey was magical and included a 12 mile stretch
along the PCT/JMT that we both agreed was our favorite hike ever.

You have been at this a long time. What keeps you inspired?
We pledged 20 years ago to keep climbing until we conquered diabetes for
Kate and friends we have made along the way, including a friend of Kate’ssister Sarah at Middlebury College, Murphy (“Murph”) Roberts, a great
person and avid adventurer who experienced a seizure related to his T1D
and passed away. We joined with the Roberts family to #senditformurph and#finishmurphsclimb. We keep climbing for Murph and with the hope that
Kate and millions of others will finally have a day without T1D.

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