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[IPp] Is BCG a cure for diabetes? The long road to acceptance



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http://www.latimes.com/health/boostershots/la-heb-diabetes-bcg-vaccine-06252011,0,3306778.story

Is BCG a cure for diabetes? The long road to acceptance

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[image: Dr. Denise Faustman and her colleagues hope eventually to cure
diabetes.]

Dr. Denise Faustman (center) and her colleagues hope eventually to cure
diabetes. (Graham Ramsay/Harvard Medical School)

By Thomas H. Maugh II, Los Angeles Times/For the Booster Shots blog

June 25, 2011, 11:54 a.m.
The first trial in a handful of humans has suggested that injecting patients
 with Type 1
diabetes<http://www.latimes.com/topic/health/diseases-illnesses/diabetes-HEDAI0000022.topic>
with
 an inexpensive
vaccine<http://www.latimes.com/topic/health/vaccines-HEDAR00000154.topic>
normally
 used to
preventtuberculosis<http://www.latimes.com/topic/health/diseases-illnesses/tuberculosis-HEDAI0000083.topic>
 can block destruction of
<http://www.latimes.com/health/la-he-bcg-diabetes-20110625,0,6341862.story>

insulin<http://www.latimes.com/topic/health/human-body/insulin-HHA0000095.topic>-secreting
pancreatic cells in humans and allow regeneration of

thepancreas<http://www.latimes.com/topic/health/human-body/pancreas-HHA0000092.topic>.
Such a finding, if confirmed and expanded on, could lay the foundation for
freeing the estimated 1 million U.S. Type 1 diabetics from their daily insulin

shots<http://www.latimes.com/topic/health/health-treatments/insulin-injections-HETHT00000020.topic>.
It brings up a word that is rarely or never used in considering the disease:
"cure." Such an outcome is still a long way in the future, but Dr. Denise
Faustman ofMassachusetts General

Hospital<http://www.latimes.com/topic/health/hospitals-clinics/massachusetts-general-hospital-ORGHC0000014.topic>
has
already come a long way in her quest to find a new treatment paradigm for
diabetes.

Researchers have always assumed that insulin-secreting cells could never be
regenerated. Once they are gone, they are gone forever, the theory held.
Scientists have thus focused on ways to prevent their loss -- such as by
developing vaccines that will halt the immune

system<http://www.latimes.com/topic/health/human-body/immune-system-HHA000031.topic>'s
attack on the pancreas before all the cells are destroyed -- or by
transplanting replacement cells from a donor. The first approach has not yet
shown much success, and the second has provided only limited benefits.
Insulin-secreting cells for transplants are difficult to obtain in quantity,
provoke a strong immune response and require immunosuppressive drugs. They
can "cure" diabetes, freeing patients from their insulin secretions, but the
benefits often disappear with time.


   -

Faustman started out as a transplanter, learning her technique from Dr. Paul
Lacey of Washington University of St. Louis, a pioneer in the field. When
she came to Mass General in 1985, she was confident that she could do the
transplants better than other researchers and that her attempts would
succeed. For one of the few times in her life, however, it turned out that
she was wrong.

She decided to go back into the lab and attempt to figure out why the
transplants were failing. Most researchers had studied transplants in mice
in which the pancreas was artificially destroyed. Faustman decided to look
at mice that, like humans, had a strong propensity to develop diabetes
naturally. She found that the transplants failed in those animals just like
they had in her human trials, and she eventually determined that the
rodents' immune systems were attacking the transplanted cells just like they
had their own pancreases.

Eventually, she developed a two-pronged attack. First she injected the mice
with Freund's Complete Adjuvant, a mixture of water, oil and parts of dead
bacteria that is sometimes used to increase the power of vaccines. The
adjuvant overstimulated the immune cells that were attacking the pancreas,
causing them to self-destruct. She also injected the rodents with BCG, known
formally as bacillus Calmette-Guerin, which has been used for 80 years as a
preventive for tuberculosis. It stimulated the production of another immune
component, called tumor necrosis factor or TNF, that kills the cells that
were attacking the pancreas.

Faustman's goal was simply to prevent the attack on islet cells of the
pancreas so that a new transplant could have a chance to take hold. To her
great surprise, however, the treated mice began producing insulin again -- a
finding that contradicted everything researchers believed about diabetes.
Eventually, however, other labs were able to replicate her results.

In subsequent papers, Faustman showed that the new insulin-secreting cells
were being produced by the spleen, a fist-sized organ that plays a crucial
role in recycling
blood<http://www.latimes.com/topic/health/human-body/blood-HHA00006.topic>
cells.
First, she demonstrated that the cure of the mice could be accelerated by
injecting extra spleen cells into the animals. Then she transplanted male
spleens into female mice undergoing the treatment and demonstrated that the
insulin-producing cells were male in origin.

Very little research has been conducted in humans about what happens to
patients after their spleens have been removed for medical reasons. But
Faustman found two studies, one of British patients with pancreatitis and
one of children with beta-thalassemia, in which their spleens had been
removed. In both groups, many of the patients developed diabetes within five
years after their surgery. These findings suggest that the spleen plays a
key role in regulating glucose uptake.

Faustman had great difficulty obtaining research funds because her ideas
were so contrary to the prevailing wisdom. One person who believed in her,
however, was Lee A. Iacocca, the former chief of Chrysler Corp., whose wife
Mary died of diabetes. Iacocca wrote her a check for $1 million and by 2006,
his Iacocca Family Foundation had raised more than $11 million for her
research.

She is now gearing up for a larger, phase 2 clinical trial of the technique.
More information about her research can be obtained
here<http://www.faustmanlab.org/> and
those interested in participating in the trials can e-mail her at
email @ redacted But be warned there is already a long waiting
list.

Rachel - email @ redacted

http://www.google.com/profiles/rachelandcole<http://www.google.com/profiles/rachelandcole#>
https://www.facebook.com/AllBrightPhotography
.
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