Dr. Faustman Update Summer/Fall 2009

Updates Summer/Fall 2009 Updates Summer/Fall 2009

Summer/Fall 2009 Ben Rosenthal Tom Hewson At 17, a mature understanding of the importance of a cure After living with type 1 at age 17, he says that keeping on diabetes for 73 years, Two Ways You top of his condition is just “part Tom is ready for a cure. Updatesfrom the Faustman Laboratory at Massachusetts General Hospital of life”. But when Susan, Ben Can Help and his step-father, Ted, learned Please support the ongoing t age 11, while attending about Dr. Denise Faustman’s research of our lab with a research towards a cure of type A summer camp on the Jersey tax-deductible donation. The Diabetes Reversal Challenge 1 diabetes at Mass General, they Shore, Tom recalls developing Every gift makes a difference The Unique Clinical Trial at the Faustman Lab immediately took notice — and an unquenchable thirst, a for patients … today and have been following the trial for telltale sign something was tomorrow. he Faustman Lab at elevating TNF levels destroys the BCG closely ever since. “There is so wrong. Shortly thereafter he was T Massachusetts General autoreactive T-cells, allowing much research on diabetes going diagnosed as a type 1 diabetic 1. To make a secure online Hospital, run by Denise L. the insulin-producing cells of donation, please visit and has been insulin-dependent the years. In spite of his vigilance Faustman, MD, PhD, is moving the pancreas to regenerate and on. What’s so attractive about Dr. www.faustmanlab.org and and diligence, however, he has Faustman’s trial, however, is that since 1936. click on “Support” rapidly through the clinical trial produce insulin. TNF in mice also it addresses the source of type 1 He recalls how scary it was had eye and heart complications challenge to test and possibly elevates a good population of diabetes by eliminating the cells at age 11 to learn that his life and, from time to time, has 2. You may make a gift establish a vaccine using a generic T-cells, thus restoring the immune that cause the disease,” says Susan, depended on daily injections suffered with temporarily by check (payable to drug, Bacillus Calmette-Guérin system to near normal. In other who met Dr. Faustman when Susan and urine tests, a strict diet disabling hypoglycemia. “Massachusetts General (BCG) to reverse type 1 diabetes. words, the treatment literally served on the board of the Juvenile and management of all the “Diabetes has a bright side Hospital – Cure Diabetes The experiments have moved from reverses type 1 diabetes, at least Now”) and mail your encumbrances that came with and a dark side,” he says. “You mice to a clinical trial in humans, in a mouse model of diabetes. In move BCG to the public rapidly Diabetes Research Foundation. check to: en Rosenthal’s mother, Susan The diagnosis, she says, was Ben recently returned from the new life regimen. There can live a nearly normal lifestyle. and the testing has passed every laboratory experiments, TNF also if the drug is indeed found to be BBenford, learned her son “shocking, terrifying”. Though she an internship in Dar es Salaam, were no disposable syringes or However, not mastering the MGH Development Office research milestone ahead of destroys the autoreactive cells in safe and effective in patients with had diabetes when he was 13 knew it was a treatable disease, Tanzania, where he worked in insulin pens in those days. It intricacies of your own self- Attn: Jocelyn Hoey schedule — an astonishing feat for human blood samples. TNF does type 1 diabetes. Our Phase I safety months old. He had lost a quarter she worried constantly when he a diabetes clinic, assisting a was necessary to sterilize a glass treatment can be fatal. You must 165 Cambridge St., Suite 600 any clinical research project. not harm the normal, healthy study is following our enrolled of his body weight, was urinating fell asleep, in particular, because physician who treats adults and syringe and needle in boiling pay attention every hour of every Boston, MA 02114 The Phase I safety trial in T-cells that help fight infection, patients over months looking for frequently and was hungry and she didn’t know if he was simply children with type 1 diabetes. water before each use. Drops of day, but simultaneously think people with type 1 diabetes is leaving the immune system intact. changes in the T-cells and also On the memo line of you irritable. “Until then, he was tired or if his insulin levels were There, the patients “get a fraction urine were put in a test tube with positive thoughts and live life to near completion. The next step The human clinical trials we are testing the reliability of our blood check, please write: “Type 1 the fullest.” an easy child, and suddenly dangerously low, which could of the insulin and monitoring water and a reagent, then heated diabetes research”. is to find, in a Phase II study, the conducting seek to expand these tests for tracking disease-causing everything turned on its head,” lead, potentially, to a coma or even supplies they need to keep their to develop a color indicative of Tom adds, “Over the years, possible dose and frequency findings in human subjects. T-cells. recalls Susan. “I was able to detect death. diabetes under control — it is so its sugar content. medical scientists have brought How can I learn more of administration of BCG The BCG trial is also unique The BCG trial is one of the few that something was wrong mostly “He was too young to speak, so much less than what I get as a Since Tom began taking insulin new understanding about the about this research? vaccinations that will benefit since BCG is a generic drug translational studies in human because I already had another I was doing a lot of guesswork,” patient in the U.S.,” he says. As a 73 years ago, he has benefited cause, care and possible cure patients with type 1 diabetes. that has been used widely as a testing where the animal data child, who was healthy. I knew that Susan recalls. result, average life expectancy for greatly from the many new for diabetes. Many research 1. Please log onto our web What makes these trials vaccine for more than 80 years in showed disease reversal in diabetic site: www.faustmanlab.org Ben’s behavior and his symptoms By the age of eight, Ben was diabetics in Africa is far lower than device developments, delivery groups are active today pursuing unique? First, unlike other humans. Currently, BCG is used mice that had hyperglycemia, not 2. E-mail us at diabetestrial@ different, promising approaches were totally abnormal.” able to monitor himself. Today, it is in America. systems and new types of insulin. partners.org immunosuppressive therapies for in small doses as a vaccine against just in mice with normal blood The experience made Ben feel Glucose monitors have enabled to a cure. As the possibility 3. Call us at 617-726-4084 autoimmune diseases that harm tuberculosis, and it is used in sugars and with a predisposition lucky to have received the care he patients to self-manage their of a cure appears closer than both healthy and disease-causing larger doses as a bladder cancer to diabetes. Therefore, this human Faustman Lab in the News! has, he says, but it also convinced diabetes more effectively. Now in ever at the Faustman Lab, I Thank you for joining us in T-cells, this treatment appears to therapy. Because it has been trial at Mass General is designed him how important a cure — of the his mid-80’s, Tom is still active, encourage everyone to support the fight against diabetes. provide a way to achieve “targeted used for so long and in so many to treat people with established U.S. News and World Report has included Dr. Faustman in kind Dr. Faustman is pursuing — swims almost daily, and follows this important and promising removal” of only autoimmune humans, the safety of this vaccine type 1 diabetes unlike most human Warmly, a recent feature entitled, “Pioneers of Medical Progress” would be, especially in developing a rigorous intensive therapy research. Its success could disease-causing cells. is well-established. This fact allows testing that focuses only on not (August 2009). Dr. Faustman is honored to be included countries like Tanzania where the for his diabetes. He estimates bring enormous benefits to the BCG works by causing the us to move more quickly through yet diabetic patients at risk for among the 14 research-scientists described in the article lack of access to insulin makes the he has had about 40,000 finger American healthcare system and release of a natural protein in the safety studies compared to clinical the disease or newly diagnosed as “cutting-edge researchers”. disease more immediately life- sticks (blood samples) and about to millions of diabetics around Denise L. Faustman, body called tumor necrosis factor, trials that test new drugs. diabetics with a short time period threatening. 85,000 insulin injections over the world.” MD, PhD or TNF. In mice, temporarily With a generic drug, we can of high blood sugars. Updates Summer/Fall 2009 Updates Summer/Fall 2009

BCG Therapy At Work regulatory and manufacturing 1 diabetes are established, we will the possibility to show meaningful processes to proceed in unison and hire our own personnel to perform results in terms of the effects BCG any people have asked us Therefore, we designed a diabetes allowed us to design an in time-efficient ways. daily to weekly inspections of the has on diabetes. M how the BCG therapy works research program to not only intervention to kill the cells that manufacturing process. These to eliminate type 1 diabetes. Below identify “bad” T-cells in humans cause disease. Step 2: Set Up inspections will ensure that the Step 6: Establish a Data is an explanation of how the BCG with diabetes but to devise ways Cure Diabetes Now is a rapid Manufacturing of BCG product manufacturing process is Safety Monitoring Board therapy finds the “bad” disease- to specifically kill those cells. One clinical translation program For Phase II, we will need to re- tightly controlled and meets For Phase II testing, we will causing cells and eliminates them sub-population of these cells has designed to safely test this package or manufacture BCG so it FDA standards. assemble a Data Safety Monitoring in type 1 diabetic blood. a cellular defect that makes these therapeutic concept in humans comes to the clinic in small vials Board (DSMB). This group will have cells susceptible to death in the with type 1 diabetes. We are that represent one easy dose per Step 4: Hire Director of access to data from the clinical How are autoreactive presence of elevated levels of TNF. using BCG, a generic drug that is vial. Currently for Phase I, Mass Regulatory Operations operations manager and will T-cells detected? This discovery, first in mice and inexpensive to produce and has a General pharmacists take large The director of regulatory analyze the data for both positive There are many different then in humans, set the stage for proven safety record, to cause the bottles of high-dose BCG and then operations will oversee the and negative side effects that might technologies to detect the “bad” us to design targeted ways to kill patient’s own body to temporarily dilute the drug to create one dose regulatory details of the trial. This require early clinical reporting. The T-cells of autoimmunity. The the disease-causing cells while produce elevated amounts of TNF and load that dose into a syringe. person will make sure the clinical DSMB will need to have expertise diabetes research community sparing the healthy cells. The goal in the hopes that this will eliminate Due to the increased number of documentation of the trial meets the in vaccine trial design and vaccine can, under certain circumstances, was to find a treatment that would one population of disease-causing patients who will be enrolled in recordkeeping standards that are therapies seeking regulatory identify individual “bad” T-cells interfere with the protein pathways cells in type 1 diabetes. In Phase Phase II, we will need to manage necessary for submission to the FDA approval. with a technology that uses proteins of the disease-causing T-cells, but II of the clinical trial, we will start the dosing in a more formalized at all stages of clinical testing. called “tetramers”. These protein not the normal T-cells. Identifying the important process of testing process. In addition, the FDA Step 7: Establish Large-Scale, structures, which can be made to differences in the proteins between the dose and frequency of drug will likely require that the drug be Step 5: Design Phase II Automated Blood Handling Process glow, bind to the “bad” T-cells and the “bad” T-cells and the normal administration to eliminate the packaged and manufactured in the Clinical Trial The Phase II trial will include can then be detected using a device T-cells of people with type 1 disease in diabetic patients. same way it would potentially be For Phase II, we will design a trial many more patients than the Phase called a “flow cytometer,” which distributed to the public. We will that is able to detect BCG’s effect on I trial. Therefore, the Faustman allows us to visualize and count the also need to establish state-of-the- established diabetic patients — in Immunobiology Laboratory will glowing particles. art manufacturing processes that particular, the best dose and timing need to have the capability to The Nuts and Bolts of Phase II of meet the highest standards. BCG of drug administration. How we handle more blood specimens and How does BCG or TNF has been around for so many years design Phase II will be dictated in will need to expand its engineering kill only the “bad” T-cells? the Cure Diabetes Now Clinical Trial that the current manufacturing part by the data in Phase I and also efforts and platforms to be ready The process of eliminating only process will not be approved by the by input from the FDA, our advisors to process the increased number the “bad” T-cells has evolved over The Cure Diabetes Now Phase I results are likely to be published in early 2010. FDA for a new indication. Setting up and the clinical trial teams at MGH. of patient blood samples. Our staff two decades and is based on basic BCG manufacturing is a critical step The FDA will likely request that a of engineers and bench scientists science work performed in the Our goal is to initiate the three-year, Phase II program without delay. We want to share in making every piece of data we larger number of patients (known will require at least six months of Faustman Lab and elsewhere. with you some of the steps we will take to begin the next, exciting phase of testing obtain from human experimentation as “sample size”) be enrolled in the training prior to the arrival of the About 20 years ago, Drs. Faustman with BCG count in Phase II. trial and that we perform long-term first clinical samples in Phase II. The and David Nathan, director of the the BCG therapy when we have funding. follow-up with trial participants. automated blood handling process MGH Diabetes Center, set up one Step 3: Set Up Enrolling/testing large numbers of yields highly pure T-cells from of the first clinical trials on the Step 1: Set Up the a trial that fits with regulatory to assemble a highly specialized Manufacturing Oversight patients and then following their human blood. Some of these pure U.S. east coast at Mass General FDA Regulatory Team constraints specifically dictated team of professionals who have had The FDA will have strict status for a long time can make trials T-cells are the autoreactive T-cells to transplant islets. During this A critical aspect of Phase II will by the FDA branch that regulates success with vaccine development requirements for the manufacturing very costly. Therefore, we will work that cause diabetes. The automated transplantation work, the data be to hire experts in vaccine drug vaccines. In addition, the team and the complex regulatory process that include rigorous with biostatisticians to design a trial blood-handling process allows us revealed that the transplanted islet development to ensure that the will help to do all the necessary processes. They will assist Mass documentation of that that is as streamlined as possible to monitor, in an individual patient, cells were killed by a recurrence of trial complies with Federal Drug paperwork from the viewpoint of General in making presentations to process. Once the contracts for so that we enroll enough patients the burden of autoreactive T-cells the disease. This suggested the type Administration (FDA) procedures. the FDA proposals highly regulated the FDA and will serve to maintain manufacturing and packaging BCG to achieve FDA standards while that are predicted to decrease with 1 disease was still active years after The team of experts will design process. Therefore, we will need data integrity in reporting and follow for the new purpose of treating type ensuring that our sample size has optimized BCG therapy. the diagnosis. Updates Summer/Fall 2009 Updates Summer/Fall 2009 www.faustmanlab.org