Promising Results of Phase I Diabetes Trial

ScienceDaily (June 26, 2011) — Promising results of the Phase I clinical trial of the generic drug BCG (bacillus Calmette-Guerin) to treat advanced type I diabetes were announced June 26 at the American Diabetes Association scientific sessions in San Diego. A research team led by Denise Faustman, MD, PhD, director of the Massachusetts General Hospital (MGH) Immunobiology Laboratory is presenting two abstracts (No. 2240-PO and No. 0057-LB) -- the first which describes the apparent reproduction in human patients of the mechanism that reversed type 1 diabetes in a mouse model and the second proposing that lack of a key part of that mechanism may explain why recent trials of an antibody-based diabetes therapy were not successful. The Iacocca Foundation has been the primary supporter of this work.

"We found that even low doses of BCG could transiently reverse type 1 diabetes in human patients," Faustman says. "One of the key components of this study was our development of a way to measure the death of the autoreactive T cells that destroy the ability of the pancreas to produce insulin. Not only did we observe and measure the death of these self-targeting immune cells, but we also saw evidence of restoration of insulin production even in patients who've had type 1 diabetes for more than a decade."
A generic drug with 90 years of safety data, BCG is currently approved by the U.S. FDA for vaccination against tuberculosis and for the treatment of bladder cancer. BCG is known to elevate levels of the immune modulator tumor necrosis factor (TNF), which previous work in Faustman's lab showed can temporarily eliminate the abnormal white blood cells responsible for type 1 diabetes in both humans and mice. The Phase I double-blinded clinical trial enrolled six long-term type 1 diabetes patients, diagnosed for an average of 15 years. The participants were randomly assigned to receive two injections of either BCG or a placebo spaced four weeks apart.

Blood samples from the participants with diabetes were also compared with samples from six nondiabetic participants and with reference samples from 75 additional individuals with diabetes and 15 without. Four measurements were analyzed for each sample -- levels of autoreactive T cells; levels of the regulatory T cells that help control the immune response; levels of GAD autoantibodies, which are a marker of pancreas activity; and levels of C-peptide, a marker of insulin secretion.

Most participants treated with BCG showed increases in both the death of autoreactive T cells and in levels of the protective regulatory T cells. A temporary but statistically significant elevation in C-peptide levels, suggesting a restoration of insulin production, was also observed in the BCG-treated patients. Unexpectedly, the same responses were seen in one of the placebo-treated patients who, after enrolling in the study, coincidently developed infection with the Epstein-Barr virus, which is known to induce expression of TNF.
"These data support our hypothesis that BCG may benefit human type 1 diabetes by boosting TNF levels," says Faustman. "The data from the EBV-infected patient show that induction of TNF expression from diverse sources may have been a missing component in two recent, unsuccessful Phase III trials that tested antibodies against the immune molecule CD3 in type 1 diabetes patients. Those trials were specifically designed to avoid reactivating any latent EBV infection, but blocking EBV activation could also block TNF expression."

In addition to providing major funding for the now-completed Phase I trial, the Iacocca Foundation has committed to a leadership role in the Phase II clinical trial that was initiated at MGH earlier this month. Currently $8.5 million has been raised out of a total of $25 million needed to conduct the Phase II study over the next three years

The Stories of Chronic Disease

I am in the habit of sharing my online experience with anyone who might happen to visit this blog.

I offer up this oldie by goodie; "Scope " a blog filled with medical news from the Stanford School of Medicine. The blog has current information on nutrition, ethics, healthcare, infectious disease, cancer, medicine and research. I have integrated a bit of Scope into my morning ritual; first a nice cup of coffee, then off to an interesting and pleasurable blog experience.

Today's contributor at Scope is Michelle Brandt who writes on the topic of rare disease, including a link into the world of chronic illness. A world that anyone living with chronic HCV is all too familiar with.

In Ms. Brandt's words; "An estimated 25-30 million Americans have a rare disease, defined by the National Institutes of Health as a condition affecting fewer than 200,000 persons. I happen to be a member of this most unfortunate club (I was diagnosed with a rare blood disorder a decade ago), so I took notice yesterday when the company Inspire posted a compilation of narratives (.pdf) written by other patients living with chronic illness" I hope you take a quick glance at Ms. Brandt's complete entry

I followed her suggestion and soon became engrossed in each personal account of the pain, frustration, and valuable wisdom experienced only by people who live with a disease that evolves into a chronic illness. That's the key, isn't it ? First the diagnosis, a disease, no cure, chronic, forever. This serious diagnosis can only be processed in stages, with the latter taking on a life of its own.

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When diagnosed the patient's shock can lead to a delayed understanding of the gravity of the diagnosis. While still straining against the weight of heavy news being heaped upon their shoulders the patient encounters the added severity of the word chronic. The patient has just been slammed twice with one diagnosis, although not simultaneously. The term "Chronic" takes its time to wriggle into mind of the patient. It starts as just a word, it's a dull blade slowly being sharpened. The patient heard: disease...no cure... They soon realize that "chronic" means illness forever.

Unfortunately chronic illness is most often endured alone in the body and mind of the patient. It's human nature to try not to disturb or upset the balance in the lives of those we love. They often suffer in silence as not to interfere with those living outside their world. Yes, initially family and friends are supportive, but as time passes the disease becomes the norm. The outside world becomes immune to the daily struggles of living with a chronic illness. The scars are not as apparent, in some cases invisible, as with some forms of chronic disease.

However, what emerges from the pain is the wisdom only won in the face of adversity, the chronic illness takes its rightful place in the rhythm of life. Sometimes the reality of chronic disease becomes mundane. The unnoticed heroes continue their triumph over life's challenges all the while quietly carrying their illness along with them. Until the day comes when the patient must come to embrace dependence on family and friends.

Please visit the linked site which is appropriately named; "Inspire".