Dr. Denise Faustman

Denise Faustman, is a U.S. physician and medical researcher. An associate Professor of Medicine at Harvard University, her work specializes in Diabetes mellitus type 1 (formerly called juvenile diabetes). She has worked at Massachusetts General Hospital in Boston since 1985. Image File history File links Denise_Faustman. ... Image File history File links Denise_Faustman. ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from... The Doctor by Luke Fildes This article is about the term physician, one type of doctor; for other uses of the word doctor see Doctor. ... Harvard University (incorporated as The President and Fellows of Harvard College) is a private university in Cambridge, Massachusetts, USA and a member of the Ivy League. ... Diabetes mellitus type 1 (Type 1 diabetes, Type I diabetes, T1D, IDDM) is a form of diabetes mellitus. ... This article is about the disease that features high blood sugar. ... Massachusetts General Hospital (often abbreviated to Mass General or just MGH) is a teaching hospital of Harvard Medical School and biomedical research facility in Boston, Massachusetts. ... Nickname: Location in Massachusetts, USA Coordinates: , Country United States State Massachusetts County Suffolk County Settled 1630 Incorporated (city) 1822 Government  - Mayor Thomas M. Menino (D) Area  - City  89. ... Year 1985 (MCMLXXXV) was a common year starting on Tuesday (link displays 1985 Gregorian calendar). ...

Research

Faustman's research is based on the observation that autoreactive T cells, that is, T cells programmed to attack the body's own cells and tissues, are more sensitive to the effects of TNF-alpha (TNF-α), a cytokine that influences the immune system. TNF-α is a strong promoter of inflammation, and several treatments have been developed to block the effects of TNF-α in chronic and autoimmune diseases, including adalimumab, infliximab, and entanercept. However, side effects of these drugs include flare-ups of autoimmune symptoms. T cells are a subset of lymphocytes that play a large role in the immune response. ... In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Adalimumab (Humira®) is the third TNF antagonist (after infliximab and etanercept) to be approved in the US. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab is a mouse-human chimeric antibody and etanercept... Infliximab (brand name Remicade®) is a drug used to treat auto-immune disorders. ...

Under some conditions, TNF-α causes T cells to undergo apoptosis, or programmed cell death. Autoimmune T cells are more sensitive to TNF-α and undergo apoptosis more readily than normal T cells when exposed to TNF-α. Faustman's hypothesis, somewhat contrary to conventional thinking, is that blocking TNF-α actually promotes the survival of undersirable autoreactive T cells, and that autoimmune diseases should be treated by stimulating TNF-α to trigger apoptosis in self-destructive autoimmune T cells. [1] A section of mouse liver showing an apoptotic cell indicated by an arrow // Apoptosis is a process of deliberate life relinquishment by a cell in a multicellular organism. ...

Former Chrysler chairman Lee Iacocca, whose wife died of type-1 diabetes complications and who has declared a desire to see the disease cured in his lifetime, is a patron of her work. After Faustman was denied funding by the JDRF, The Iacocca Foundation provided an $11.5 million dollar grant which both supported Faustman's work, and is being used for a clinical trial to be conducted by Harvard researcher David Nathan. This trial will not use spleen cells but only bacillus Calmette-Guerin (BCG), a weakened strain of bacteria that is used in the prevention of tuberculosis and in the treatment of bladder tumors and bladder cancer. BCG induces TNF-α. In previous human trials, it has not been shown to have a therapeutic effect in type 1 diabetics. Faustman hypothesizes that the correct dosing of BCG for diabetics has not been utilized in previous trials. As part of her research, she is seeking to define a dose that might have a therapeutic effect in the clinical trial to be led by Dr. Nathan. For other uses, including the Chrysler Brand, see Chrysler (disambiguation). ... Lido Anthony Lee Iacocca (born October 15, 1924) is an American industrialist most commonly known for his revival of the Chrysler brand in the 1980s when he was the CEO. Among the most widely recognized businessmen in the world, he was a passionate advocate of U.S. business exports during...

Faustman's research has been profiled in the New York Times on November 9, 2004 and March 24, 2006, and in the Wall Street Journal on March 24, 2006. The New York Times is an internationally known daily newspaper published in New York City and distributed in the United States and many other nations worldwide. ... is the 313th day of the year (314th in leap years) in the Gregorian calendar. ... Year 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... is the 83rd day of the year (84th in leap years) in the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday (link displays full 2006 calendar) of the Gregorian calendar. ...

Recent Controversy

Research

This approach was recently tested in non-obese diabetic mice (NOD mice), a strain of mice that spontaneously develops Type 1 diabetes. Injecting the mice with a common inflammatory agent (Freund's adjuvant) and a preparation of spleen cells allowed the beta islet cells to regenerate. [2] Diabetes mellitus type 1 (Type 1 diabetes, Type I diabetes, T1D, IDDM) is a form of diabetes mellitus. ... Freunds adjuvant is an antigen solution emulsified in mineral oil, used as an immunopotentiator (booster of the immune system). ... Beta cells are a type of cell in the pancreas in areas called the islets of Langerhans. ...

The adjuvant increased the production of TNF-α , which reduced the number of autoreactive T cells and allowed for islet cell regrowth. Faustman hypothesizes that this regeneration may be attributed in part to the re-differentiation of the spleen cells, a position that continues to be debated. Embryonic stem cells differentiate into cells in various body organs. ...

The Funding Quagmire

There is no more debate as to the cause of Type 1 Autoimmune Diabete. It is caused by rogue T cells that attack healthy tissue. In the case of Type 1 Autoimmune Diabetes, the healthy tissue under attack are the beta cells that regulate and produce insulin. Faustman's protocol of Freund's adjuvant, along with the spleen cells, was effective in curing even mice with end-stage diabetes. In her human trial, scheduled for early 2008, she plans to use BCG to kill the rogue T-cells that maintain the diseased state of autoimmunity. CFA and BCG affect rogue T-cells in a peculiar way, they induce cell apoptosis, a kind of cell suicide. Normal T-cells remain unaffected. The research is promising because it is hoped that once the bad T-cells are gone, regeneration of the beta cells will ensue.

However, a debate continues over the source of the islet cell regeneration even though it has been proven by countless follow-up research that it does occur. An article in Diabetes Health details the backstory of the controversy.[3] In the article it is revealed that the JDRF listed Dr. Faustman's work in their annual 990 report even though it rejected every grant for her project. Seeing a potential breakthrough that remained unfunded, Lee Iacocca stepped in and formed JoinLeeNow.org. This organization was founded for the purpose of moving Dr. Faustman's research forward. They have pledged to grant $10,000,000 over several years for the phase 1 trial.

Researchers from three laboratories funded by the Juvenile Diabetes Research Foundation confirmed her success with mice and published paper in the March 24, 2006 issue of Science, but suggest that the proliferation of existing pancreatic stem cells may have been responsible for the success of the treatment. More importantly through, regeneration did occur once the rogue T-cells were removed, it just wasn't obvious where the regeneration was coming from. However, when one has a wound, generally no one doubts the healing process just because one cannot pinpoint exactly how and by what mechanism the healing process occurrs. The JDRF funded researchers did not find that adult spleen cells played a role in the regeneration of islets. This, however, is a red herring, because the broader, more important issue is that regeneration did occur, even in their own research and has been replicated again and again in at least five more papers since then [4]. Faustman responded to the criticism in an article in the Wall Street Journal that "The pancreas is too smart to cure itself in only one way," and stated "I think there will be many sources of regeneration, and we're only at the beginning of understanding what they are." This article needs to be wikified. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates[2]. It is both exocrine (secreting pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin, glucagon, and somatostatin). ... Adult stem cells can be found in all adults and young adults. ...

Coverage of the financing debacle has been widespread. The New York Times, in a March 24, 2006 article titled "A Controversial Therapy for Diabetes Is Verified," states that "Three groups of scientists report today that they independently replicated a controversial finding." [5] Similarly, The Wall Street Journal's article ran with the headline, "After Initial Rejection, Scientists Back Work on Cure for Diabetes."

A newspiece that ran in Science on that same day, however, says ""Three separate attempts have failed to replicate promising results that electrified the diabetes community 2 years ago." [6] In addition, the piece reported that ""because the three groups could not detect spleen-derived beta cells, and because treatment with CFA and islets alone yielded the same results as when spleen cells were added to the mix, the groups attribute these cures to CFA and temporary islets," and that "using CFA to cure mice is probably not relevant to humans." But nobody has ever measured BCG dosage and autoreactive cell death in repeated dosages as Faustman plans to. A grassroots campaign to raise money through Joinleenow.org from the Iacocca Foundation plans to bring Faustman's work to human trials.

Since then, a group from the National Institutes of Health has replicated her work in mice who have type 1 diabetes and Sjogren's disease. This laboratory was also able to confirm a role for a splenic stem cell in regeneration. The results are part of a poster presentation by Tran et al. (Abstract # 1202-P) at the June 2006 American Diabetes Association (ADA) Meeting [7]. Similarly, a Japanese group also presented corroboratory findings at the ADA meeting, presented by Okubo et al (Abstract # 1193-P).

Partial bibliography

• Kuhtreiber WM, Kodama S, Burger DE, Dale EA, Faustman DL (2005). "Methods to characterize lymphoid apoptosis in a murine model of autoreactivity". J Immunol Methods 306 (1-2): 137-50. PMID 16242708. 

• Kodama S, Davis M, Faustman DL (2005). "The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis". Cell Mol Life Sci 62 (16): 1850-62. PMID 15968469. 

• Kodama S, Faustman DL (2004). "Routes to regenerating islet cells: stem cells and other biological therapies for type 1 diabetes". Pediatr Diabetes 5 Suppl 2: 38-44. PMID 15601373. 

• Ryu S, Kodama S, Ryu K, Schoenfeld DA, Faustman DL (2001). "Reversal of established autoimmune diabetes by restoration of endogenous beta cell function". J Clin Invest 108 (1): 63-72. PMID 11435458. 

• Kodama S, Kuhtreiber W, Fujimura S, Dale EA, Faustman DL (2003). "Islet regeneration during the reversal of autoimmune diabetes in NOD mice". Science 302 (5648): 1223-7. PMID 14615542. 

• Begley, S. After Initial Rejection, Scientists Back Work On Cure for Diabetes. Wall Street Journal. (Eastern edition). New York, N.Y.: Mar 24, 2006. pg. B.1

• Jensen, Martin. "Why Did the JDRF Try to Discredit Cure Research?". Diabetes Health. San Francisco, CA: May 2005.

External links

• Gina Kolata. "A Controversial Therapy for Diabetes Is Verified", The New York Times, March 24, 2006. Retrieved on 2006-03-27. 

• Gina Kolata. "A Diabetes Researcher Forges Her Own Path to a Cure", The New York Times, November 9, 2004. Retrieved on 2006-03-11. 

• Mass. General - Denise Faustman, MD

• Join Lee Now

• Status of type-1 diabetes cures currently in human trials. Includes Faustman's and others.

• [8]Diabetes Health article on Dr. Faustman