Indeed, very interesting. It's not a cure, obviously, but it does
to stabilize the disease in some patients. An important caveat is that
might make a useful adjuvant treatment.
A Medline search on GJ Brewer yielded 55 hits ("Brewer GJ copper"). He
appears to have a comprehensive body of work on Wilson's disease (rare
genetic disorder resulting in copper overaccumulation, with eventual
liver and neurological damage). Tetrathiomolybdate may not be widely
available--my impression is that it is still in clinical trials for
Wilson's disease. But zinc acetate is also used to treat Wilson's
disease. Zinc competes with copper for absorption from the gut. One of
Brewer's abstracts suggested anecdotally, that a vegetarian diet may
result in a mild copper deficiency that can control Wilson's disease
symptoms, but that approach hadn't been investigated. (However it also
suggested most people barely get enough copper from their diets anyway.)
Something legitimate to follow.
T.
> ----------------------------
> Copper-Lowering Drug Stabilizes Advanced Cancer in Antiangiogenesis Trial
> January 21, 2000
> Clinical Cancer Research/MedscapeWire
> _
> By depriving cancer tumors of the copper supply they need to form new {*filter*}
> vessels, researchers at the University of Michigan report they have stopped
> the growth and spread of the disease in a small group of patients with
> advanced cancer for more than a year.
> Five of six patients whose copper levels were kept at one fifth of normal
>for
> more than 90 days had no growth of existing tumors or formation of new ones,
> according to a paper published in the January issue of Clinical Cancer
> Research. The sixth had progression of only 1 tumor; all other tumors within
> her body remained stable. Twelve other patients did not achieve the target
> copper level, or could not stay at the target level for 90 days, because of
> disease progression.
> This finding is the first evidence in humans that physicians might fight
> multiple types of cancer by targeting copper as a "common denominator" of
> angiogenesis ? the process by which tumors grow the {*filter*} vessels that allow
> them to expand beyond a tiny cluster of cells.
> The copper strategy is not limited to a single type of cancer, as are other
> antiangiogenesis agents now being studied around the world. Patients in the
> phase I trial had metastatic cancer of the {*filter*}, kidney, colon, lung,
>skin,
> pancreas, prostate, throat, cartilage, {*filter*} vessels or endothelium. All had
> exhausted other conventional treatment options.
> The trial used {*filter*}doses of an inexpensive compound called
> tetrathiomolybdate (TM) to lower the patients' copper levels. TM was
> originally developed for clinical use by George J. Brewer, MD, a University
> of Michigan human genetics professor, to treat people with Wilson disease, a
> rare genetic disorder caused by excess copper. His work has shown TM to be
> the world's most potent anticopper agent, and has also demonstrated that it
> is safe to use.
> Aware of earlier research indicating that copper is important for
> angiogenesis, Brewer did work in the early 1990s on animal cancer models
> treated with TM, with encouraging results. Then, he teamed up with Sofia
> Merajver, PhD, MD, a molecular genetics researcher and oncologist at the
> University of Michigan Comprehensive Cancer Center.
> Independently, Merajver was interested in exploring the inhibition of
> angiogenesis at very early stages in cancer development. Together with
> Brewer, she designed specific animal studies that allowed the team to test
> whether TM had the ability to prevent tumors from arising in animals at
> high-risk for cancer. Her laboratory has also begun to uncover the molecular
> and cellular events involved in the inhibition of {*filter*} vessel growth by
> copper deficiency.
> Their first results from humans actually come from a trial that was designed
> only to see how well TM could reduce copper levels in cancer patients,
>not to
> test its effect on the cancer itself. At all 3 daily dose levels given in
>the
> trial, copper levels were reduced to 20% of normal in 4 to 6 weeks. Neither
> the drug nor the long-term copper deficiency produced adverse effects.
> "What began as a scientific hunch now appears to have potential as a simple
> but effective general antiangiogenesis strategy," says Brewer. "We are
> proceeding with a clinical trial aimed at accelerating TM-induced copper
> reduction and assess its effect on advanced-stage cancer. Later this
>year, we
> hope to test this approach in 100 patients with 5 types of less advanced
> cancer." Neither trial is currently accepting patients. For more
>information,
> call 1-800-742-2300, category 7882.
> Adds Merajver, "These initial results suggest that the tactic of preventing
> angiogenesis through copper deficiency holds significant promise. Through
> this and other therapies, we may one day be able to turn cancer into a
> chronic or controllable disease or to contribute to its eradication. Still,
> much more research is needed before we can know the full potential of
> antiangiogenesis."
> In recent years, researchers have found that copper is a common denominator
> to several of the key factors that activate the angiogenesis process.
> Specifically, it acts as a cofactor, or helper, to molecules known as basic
> fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF),
> and angiogenin. Without it, they can't function and construction of {*filter*}
> vessels stops.
> That's why TM makes such a good choice, Brewer explains. It binds with
>copper
> and protein, making a stable compound that can't be used by tumor cells or
> any other part of the body. Taken at mealtime, TM prevents the body from
> processing and absorbing the copper in cooking.net">food as well as the copper normally
> found in saliva and gastric secretions. Taken between meals, TM is absorbed
> into the {*filter*} and binds copper to {*filter*} protein. In either case, the
> TM-protein-copper complex does not interact with other biological molecules
> and is excreted.
> The power of TM to stop angiogenesis in cancer cells was clearly shown in a
> trial conducted by Brewer and Merajver using mice specially bred to have a
> 100% risk of {*filter*} cancer. The compound prevented cancer tumors from
>growing
> in all the mice, a remarkable achievement that encouraged the researchers to
> pursue the human trial. Animal research elsewhere using another
> copper-reducing agent was not as successful.
> As reported in Clinical Cancer Research, the trial found that 120 milligrams
> of TM per day was the most effective dose of the 3 doses tested, bringing
> copper levels to the target of 20% of baseline without adverse effects.
> Brewer and Merajver call this level a "window" that allows the body's other
> copper-based reactions, such as red {*filter*} cell function, to proceed but
> starves tumors of the copper needed for angiogenesis. Patients who stop
> taking TM have normal copper levels again within days.
> Of the 6 patients who reached the target copper level and remained on TM for
> more than 90 days, 4 are still alive after treatment periods ranging from 11
> months to 21 months. Two others have left the study but are still alive
>after
> 6 and 17 months.
> While not all patients in the trial reached the 20% target within the 90-day
> period specified, the researchers believe that increased doses of TM will
> achieve this goal in future patients. Already, the first 2 patients in the
> new phase I/II trial have seen their cancer remain stable after more than 5
> months of treatment.
> "We also believe that the earlier TM is given in the progression of a
> patient's cancer, the better it should work," says Merajver. A 100-patient
> phase II trial of TM in patients who have recently completed conventional
> therapy for {*filter*}, prostate and kidney cancer, sarcoma, and multiple
>myeloma
> is being planned for this year.
> A full-scale toxicity test of TM will also begin shortly, though the
>compound
> has shown no toxic effects in dozens of Wilson disease patients who have
> taken it to remove copper from their bodies. Toxicity data are required
> before TM can enter phase III clinical trials.
> The University of Michigan has filed for a new-use patent for TM in the
> treatment of cancer and other diseases that rely on angiogenesis. The
> university is currently in negotiations with a pharmaceutical company to
>fund
> further research, part of which will be directed at testing the efficacy of
> new compounds with similar copper-lowering effects.
> The discovery of TM's potential effect on cancer grew directly out of
> Brewer's decades-long research effort on trace metals' importance to the
> body. He began by examining the role of zinc in sickle-cell anemia, and
> unexpectedly found that zinc acetate reduced the level of copper in the
>{*filter*}
> of some patients.
> This gave him the idea to test the compound's effect on the dangerously high
> copper levels in the systems of patients with Wilson disease, a potentially
> fatal recessive genetic condition that strikes 5000 {*filter*}agers and young
> {*filter*}s each year. Finding that zinc acetate brought the patients' dementia,
> drooling, slurred speech, temper outbursts, and tremors under control if
> taken regularly, without adverse effects, he sought and received FDA
>approval
> for the compound.
> But he needed a faster-acting compound to bring copper levels under control
> quickly. That compound turned out to be TM, now in clinical trials at the
> University of Michigan General Clinical Research Center. To date, 63 Wilson
...
Copper-Lowering Drug Stabilizes Advanced Cancer