Cary Posted September 16, 2003 Share Posted September 16, 2003 Drug Developed For Rare Disease May Help Millions More As Treatment For Cancer, Autoimmune Diseases 9/10/2003 Source: University of Michigan Health System An anti-angiogenesis drug developed at the University of Michigan is showing promise in studies of three different disease families, including multiple forms of cancer. The drug, tetrathiomolybdate or TM, essentially wages war against copper, which serves to choke off tumor growth, fibrosis and inflammation. U-M researcher George Brewer, M.D., who developed the drug, will present his findings to date and report on ongoing basic and clinical TM research at the 226th American Chemical Society national meeting Sept. 10 in New York. Brewer's presentation will be part of a one-day symposium on medicinal inorganic chemistry. TM began as a treatment for Wilson's disease, a rare genetic disease that causes toxic build-ups of copper. Recent phase III clinical data show TM is more effective than other treatments at reducing the disease's effects. Realizing the key role of copper in angiogenesis, Brewer and colleagues then began exploring treatments for cancer, including breast cancer, kidney cancer and liver cancer. Currently, TM is involved in nine phase II clinical studies related to cancer, with more planned. But it doesn't end there. Brewer and colleagues are also looking into the effect of TM on inflammatory fibrosis diseases such as pulmonary fibrosis, cirrhosis, cystic fibrosis and psoriasis. "TM has the potential to be a powerful tool in fighting a wide range of diseases. While it has literally saved the lives of young people with Wilson's disease, Wilson's is a rare disease. If early results in cancer and inflammatory diseases hold their promise through the next phase of trials, there's potential for this to impact a lot of people," says Brewer, Morton S. and Henrietta K. Sellner Emeritus Professor of Human Genetics at the University of Michigan Medical School. Wilson's disease typically strikes young adults in their teens or early 20s. The condition causes copper to accumulate in the body at dangerous levels, and if left untreated can cause severe liver damage and neurological effects and eventually death. Positive results of phase III clinical studies on TM in Wilson's disease were published last winter. Brewer is currently looking for a drug company to submit it for approval by the U.S. Food and Drug Administration as an orphan drug for treating Wilson's disease. Meanwhile, patients have come to UMHS from all over the world to receive treatment through the clinical trials protocol. While the Wilson's treatment began to achieve success in the early 1990s, research at U-M and elsewhere started to uncover the role of copper in angiogenesis, or the formation of new blood vessels. This is a process that occurs normally in the body but becomes uncontrolled in cancerous cells. Researchers found copper was important to various molecules called growth factors that are necessary to the organizing process by which cells become part of new blood vessels. That launched Brewer into a new direction with TM as an anti- angiogenesis drug. He began working with breast cancer researchers, particularly Sofia Merajver, M.D., at the U-M Comprehensive Cancer Center. In 2000, they published promising results of a pilot clinical trial. From there, many more trials have begun, some of which are now reporting positive early results. "TM inhibits angiogenesis and growth factor by reducing the copper," Brewer says. "Essentially, the drug blocks the key signaling pathway, preventing tumor cells from sending signals to form new blood vessels, which thereby prevents or slows the cancer from growing or spreading." TM is made up of the elements sulfur and molybdenum. These combined elements latch on to copper in the blood and to a protein called albumin. The three-part complex formed by this bonding is then eliminated by the body. For Wilson's patients, this brings high copper levels down to normal ranges. In cancer, it creates a mild copper deficiency, which is what inhibits the tumor growth. And that led Brewer to consider whether TM would affect fibrotic diseases. In much the same way that copper deficiency inhibits the angiogenic effect in tumor cells, Brewer found it also inhibits transforming growth factor beta, or TGF-beta, the response that triggers the connective tissue growth. Additionally, studies suggest TM inhibits TNF-alpha, or tumor necrosis factor alpha, the response that triggers inflammation. "When an organ is injured, the body overreacts, and doesn't properly regulate. This causes inflammation and fibrosis to over-respond, producing diseases. With TM, we're able to shut down the excessive inflammation and excessive fibrosis that causes much of the disease after an organ is injured," Brewer says. TNF-alpha antibodies, sold as the commercial drugs Enbrel and Remicade, have been used in new treatments for autoimmune diseases such as rheumatoid arthritis and Crohn's disease. But this therapy requires regular injections of the antibodies. The next question on Brewer's plate is whether TM can do the job even easier. "We have an oral pill that's shown to inhibit TNF-alpha in mice. The concept is that for whatever diseases these antibodies therapeutically benefit, TM should be tried," Brewer says. Studies are either beginning or in the planning stages for several autoimmune diseases. One of the advantages to TM is that it carries few side effects. Studies to date show the primary side effect is copper deficiency from overtreating. This causes anemia, but is corrected by adjusting the dose of the TM. Some of the TM trials that are currently in place or being planned at UMHS and collaborating institutions include breast cancer, kidney cancer, liver cancer, esophageal cancer, mesothelioma, idiopathic pulmonary fibrosis, scleroderma, primary biliary cirrhosis and psoriasis. Quote Link to comment Share on other sites More sharing options...
cathy Posted September 16, 2003 Share Posted September 16, 2003 Hi Cary, We went to to Uof M for my dad. WE seen a pulmonologist and I asked him about Dr. Brewer and how do we get an appointment with him, he didnt seem to interested in him because I dont think he knew too much about his theory. He said "oh yeah the copper man" you really cant get an appointment with him like you do with a doctor. I wish now that I had followed through with my instincts. I wasnt aware of his developments with fibrosis, had I known I definately would have tried to get dad into a trial, because it was the fibrosis that took my dad from us. Bottom line is go with your instincts, dont let anyone talk you out of something that you think may help you. Praying for you all. Quote Link to comment Share on other sites More sharing options...
Cary Posted September 17, 2003 Author Share Posted September 17, 2003 Hi Cathy, The only thing your Onc was correct about is the fact that you can't see Dr. Brewer the same way as an ordinary doctor, but the Onc should have known TM can be obtained by any physician willing to prescribe it(which there are). Since my father started this treatment our doctor has talked to Dr. Brewer a few times on behalf of my father. I have known for quite some time that TM helps to prevent lung fibrosis(my father has not had chest radiation yet and hopefully will not have to). When my father had his Whole Brain Radiation I found out that TM can help prevent long term side effects(inflammation causing necrosis of the brain) that are commonly associated with radiation. TM can actually make the radiation treatment more effective. You can't feel guilty about not getting TM your Onc should have been more supportive and knowledgeable especially since he works right at UofM. Cary Quote Link to comment Share on other sites More sharing options...
cathy Posted September 17, 2003 Share Posted September 17, 2003 I am sitting here staring at the screen, shaking my head and I dont know what to think. All I can think of is "what if." You are so lucky to have a doctor who does his homework. I just cant understand how they just dont care. Take care of your precious dad Cary. Quote Link to comment Share on other sites More sharing options...
Tiny Posted September 21, 2003 Share Posted September 21, 2003 Cary I love the picture of your dad and son...those heads are soooo cute! Thanks for the TM information. I hope many people on the board take the time to read it and give it some consideration. Quote Link to comment Share on other sites More sharing options...
Cary Posted September 25, 2003 Author Share Posted September 25, 2003 Tiny, Thank You, I actually just enlarged their heads even more. That was me trying to give my son a haircut, well you can see how i fixed it.(who knew giving haircuts could be that difficult ) Quote Link to comment Share on other sites More sharing options...
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