Proposal : Can Autism by treated 

by removing Copper with Clioquinol?

A work in progress, exploring the pros and cons.
Copyright December 20, 2003, by the Newsletter Dad.
No claim made to existing copyrighted material listed below.


In December 2003, one scientist showed that removing copper from the body could help Alzheimers patients.  For ten years, this scientist was derided by mainstream physicians for his position.  Mainstream physicians also deride anything to do with autism.  If the removal of copper can improve the lives of alzheimers patients, will the removal help autistic children?  Autistic children show the highest levels of copper of any group of patients with neuorological symptoms. Unfortunately, the drug used successfully for the older patients is not approved for children, ironically, because of the effect it can have on the neurology.  While the problem may occur because there is insufficient data on calibrating the proper dosage for a child, one cannot experiment on children to find what dose will remove the copper from their brains without endangering some of the children. Either some other form of chelation must be found or studies must be done to show that the dangers of clioquinol are actually desired effects (the removal of copper).  Also, clioquinol was disapproved because it was not worth the risk for treating dermatitis; is it worth the risk for autism?

"Zinc changes the chemistry of the amyloid protein, giving it the rigidity to form plaques, which can't be dissolved and eliminated, he said. Copper stuck in the plaques turns oxygen into hydrogen peroxide, a toxin that destroys brain cells, and which may be responsible for the typical holes found in the brains of Alzheimer's patients."


Toxic metal levels linked to autism
Published: Feb. 28, 2013 at 12:25 PM

PHOENIX, Feb. 28 (UPI) -- Children with autism had higher levels of several heavy metals in their blood and urine compared to typical children, U.S. researchers reported.

Study leader James Adams, who directs the Arizona State University Autism/Asperger's Research Program, said the study involved 55 children with autism ages 5-16 compared to 44 controls of similar age and gender.

The study, published in the journal Biological Trace Element Research, found the autism group had significantly higher levels -- 41 percent -- of lead in their red blood cells and 74 percent higher urinary levels of lead, 77 percent higher levels of thallium, 115 percent higher levels of tin and 44 percent higher levels of tungsten.

Lead, thallium, tin and tungsten are toxic metals that can impair brain development and function, and also interfere with the normal functioning of other body organs and systems, Adams said.

A statistical analysis was conducted to determine if the levels of toxic metals were associated with autism severity, using three different scales of autism severity.

The study found 38 percent to 47 percent of the variation of autism severity was associated with the level of several toxic metals, with cadmium and mercury being the most strongly associated.

"We hypothesize that reducing early exposure to toxic metals may help ameliorate symptoms of autism, and treatment to remove toxic metals may reduce symptoms of autism; these hypotheses need further exploration, as there is a growing body of research to support it," Adams said in a statement.

Level of Trace Elements (Copper, Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism

Biological Trace Element Research
, Volume 142, Issue 2, pp 148-158
Malarveni Damodaran Lakshmi Priya, Arumugam Geetha


Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements. There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium (Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood Autism Rating Scale, n  = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children. The children with different grades of autism showed high significance (p  < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed a significant elevation (p  < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The levels of trace elements Mg and Se were significantly decreased (p  < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.

Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers

Biological Trace Element Research
June 2006, Volume 110, Issue 3, pp 193-209

J. B. Adams, C. E. Holloway, F. George, D. Quig


The objective of this study ws to assess the levels of 39 toxic metals and essential minerals in hair samples of children with autism spectrum disorders and their mothers compared to controls. Inductively coupled plasma-mass spectrometry was used to analyze the elemental content of the hair of children with autism spectrum disorders (n=51), a subset of their mothers (n=29), neurotypical children (n=40), and a subset of their mothers (n=25). All participants were recruited from Arizona. Iodine levels were 45% lower in the children with autism (p=0.005). Autistic children with pica had a 38% lower level of chromium (p=0.002). Autistic children with low muscle tone had very low levels of potassium (−66%, p=0.01) and high zinc (31%, p=0.01). The mothers of young children with autism had especially low levels of lithium (56% lower, p=0.005), and the young children (ages 3–6 yr) with autism also had low lithium (−30% p=0.04). Low iodine levels are consistent with previous reports of abnormal thyroid function, which likely affected development of speech and cognitive skills. Low lithium in the mothers likely caused low levels of lithium in the young children, which could have affected their neurological and immunological development. Further investigations of iodine, lithium, and other elements are warranted.

Background: copper and metal disorders in children with autism

Disordered Metal-Metabolism: A Primary Cause of Autism?

[This excerpt ran in FEAT on-line Dec. 20, 2000. Newsletter Dad heard William Walsh speak about this research at a support group in January 2001 and remains intrigued. Once this work is published - Walsh's website notes that Nature is considering it - it will be interesting to see if others can follow-up or replicate the following.]

Researchers in Naperville, Ill., have revealed findings that may explain the cause of autism. Biochemist, William J. Walsh, Ph.D. and Physician, Anjum Usman, M.D. presented their findings this fall concerning autistic patients' abilities to metabolize metals at the 10th Annual HRI-Pfeiffer Symposium. The Health Research Institute (HRI) has examined blood, urine, and hair chemistries for 503 patients in the autism spectrum. The study population was composed of patients diagnosed with (a) classical autism, (b) Asperger's Syndrome, or (c) pervasive developmental disorder with autistic tendencies. Metal-metabolism disorders of unusually high incidence and severity were found in all three groups.

A total of 85 percent (N equals 428) exhibited severely elevated Cu/Zn [copper/zinc] ratios (see footnote at end of release) in blood, suggesting a disorder of metallothionein (MT), a short linear protein responsible for homeostasis of Cu and Zn. The severity of the Cu/Zn imbalance was far greater than that of any other population we have studied over the past 25 years. The average Cu/Zn ratio was 1.78 (N equals 428) compared to 1.15 in a normal population (N equals 87) tested over the same time frame.

An additional 6 percent of the population (N equals 30) exhibited a pyrrole disorder associated with severe zinc deficiency. These autistic pyrolurics exhibited an average urine kryptopyrrole level of 79 mcg/dl, the highest ever observed in a defined population. Severe zinc depletion can result in improper induction and functioning of MT.

The remaining study subjects (N equals 45) included patients who were taking aggressive zinc and B-6 therapy at the time of blood sampling, which could mask the presence of a Cu/Zn or pyrrole disorder. Careful analysis of the medical histories and chemistry data indicated that 499 of the 503 autistics exhibited evidence of a metal-metabolism disorder. We believe that the remaining 4 subjects may have been misdiagnosed.

Overall, more than 99 percent of the 503 autistic subjects exhibited clear evidence of a metal-metabolism disorder. This suggests that an inborn error of metal-metabolism may be a fundamental cause of autism. To examine this possibility, the expected consequences of a MT defect on child development was investigated.

In humans, the MT family is a group of four cysteine-rich metal binding proteins that are induced and regulated in response to metal toxicity, cellular stress, neuronal development, and inflammation. Examination of the primary functions of MT and recent studies of MT-knockout mice indicate that the primary consequences of MT disorders in a newborn include:

1. Abnormal Cu and Zn levels in blood and hippocampus,

2. Impaired neuronal development, especially in the first 30 months of life, which could result in incomplete maturation of the G.I. tract and brain,

3. Absence of MT's protective detoxification of Cd [Cadmium], Pb [lead], Hg [mercury], and other heavy metals, resulting in greatly-increased vulnerability to these toxics, and

4. Impaired immune function.

The consequences of a MT dysfunction in a newborn are very similar to classic symptoms of autism, Aspergers syndrome, and PDD. For example, incomplete maturation of the G.I. tract could be responsible for the severe malabsorption and other digestive problems exhibited by most autistics. In another example, about 50 percent of the 503 autistic families in this study reported "regressive autism" in which autism symptoms appeared in a normally developing child, soon after exposure to a toxic metal. We believe that regressive autism is caused by a genetic error of metal metabolism followed by victimization by a toxic metal in the first 30 months of life. After the age of 30 months, the brain and G.I. tract may be sufficiently mature to prevent the onset of autism.

In summary, these biochemical findings suggest that an inborn error of metal metabolism (perhaps a MT disorder) may be the primary cause of autism. We are presently engaged in an experimental investigation of metal-metabolism genetics in an attempt to identify the autism gene(s).

Footnote: Serum Cu (mcg/dL) and plasma Zn (mcg/dL) levels analyzed by LabCorp and Smith-Kline-Beecham.

for more info contact:
 HRI - Pfeiffer Treatment Center

1804 Centre Point Circle, Suite 10, Naperville, IL 60563.
(630) 505-0300

The following is additional information a Newsletter Dad  wrote up for us from his notes taken when he heard Walsh speak in January.

This research implies that some children have a gene which does not permit them to remove mercury from their bodies and which impairs their immune system. The gene was latent and present in the population all along, but its effects could not be known until there was an environmental change. As the government mandated increased vaccines over the last 20 years, the amount of ethyl mercury injected into children during the first 30 months of life also increased. The effect of mercury poisoning during that period is different because the brain is still developing its neural network. A weakened immune system would also have trouble with the "whole cell" pertussis vaccine which was used in the 1990s. After 36 months, language has been sufficiently developed and the brain may be mature enough that it can sustain mercury poisoning without loss of language.

Walsh also believes that HRI will identify the gene responsible for MT dysfunction within the year and is looking at location 16P. If HRI does identify the gene, they anticipate that all newborns will have a genetic test for the MT allele, just as they do with the PKU test. If the test is positive, those children would be protected from vaccines until age three. Meanwhile, vaccination compliance rates in the general population could increase since science will eliminate the uncertainty over which children will develop autism from vaccines and parents could be reassured of general vaccine safety.

MT dysfunction could also compromise the gastrointestinal tract, resulting in susceptibility to allergies and deficiencies in enzymes which break up casein and gluten. Walsh proposes normalizing the G.I. tract and balancing the chemistry to start rehabilitating the MT deficient patient. 

HRI holds one of the world's largest databases of blood samples from autistic patients and patients with other psychiatric conditions. If its findings can be replicated by others, such as AGRE, countless children may benefit.

Walsh found the copper concentrations in the autistic patients were higher than that of any other group, including bipolar and schizophrenic patients.

The above was copied from the March 2001 AutismNews newsletter

More Details from Walsh's work on copper from the Oct 2001 DAN conference

New Hope in treating neurological illnesses by removing copper with clioquinal


Ironic Fate: Can a Banned Drug Control Metal Heavies in Neurodegenerative Diseases?

In this issue of Neuron, Kaur et al. demonstrate that iron chelation by ferritin transgene or the metal chelatory
tor clioquinol prevent oxidative damage and MPTP toxicity in mice. This raises the issue of specific iron
chelators or clioquinol for control of oxidative damage in Parkinson’s, Alzheimer’s, and other neurodegenera-
tive diseases, but not without safety concerns.

Alzheimer researchers finding new promise in old drug

By Ronald Kotulak
Tribune science reporter

December 16, 2003

An antibiotic no longer in use may be resurrected as a treatment for Alzheimer's disease, according to new findings suggesting the drug may be able to dissolve the destructive plaques in the brains of Alzheimer's patients.

The study is small and the results preliminary, but experts say the drug, clioquinol, may be the first medication to strike at the heart of the disease.

"Clioquinol is providing some symptomatic relief to patients and that's important," said Dr. Roger N. Rosenberg, director of the Alzheimer's Disease Center at the University of Texas Southwestern Medical Center in Dallas and editor of the Archives of Neurology. "And it turns out it's getting to one of the roots of the disease."

Reporting in Monday's issue of The Archives, a publication of the American Medical Association, Dr. Ashley Bush of Massachusetts General Hospital, Dr. Colin L. Masters of the University of Melbourne and their colleagues found in a nine-month study that clioquinol dramatically slowed the progression of Alzheimer's disease in 18 severely affected patients.

The disease got significantly worse in 18 comparison patients given a placebo. Patients had moderately severe to severe Alzheimer's disease.

The disease, which affects an estimated 4.5 million Americans, is increasing as more people live longer.

"There's evidence of a significant slowing of decline," Bush said. "It's not so much that the patients improved, although it's still too early to make much comment about that. These patients were quite severely affected with Alzheimer's disease. It's more that they did not deteriorate during the period of the trial. That's a big deal."

Clioquinol was chosen not because it is an antibiotic but because of its side effect: It leeches zinc and copper out of the body.

Bush theorized that when a common brain protein, beta amyloid, becomes abnormal it becomes a magnet for both zinc and copper, setting the foundation for the development of Alzheimer's disease.

Zinc changes the chemistry of the amyloid protein, giving it the rigidity to form plaques, which can't be dissolved and eliminated, he said. Copper stuck in the plaques turns oxygen into hydrogen peroxide, a toxin that destroys brain cells, and which may be responsible for the typical holes found in the brains of Alzheimer's patients.

The researchers demonstrated this model two years ago by inserting a human Alzheimer gene into mice. The brains of the mice became riddled with plaque and their behavior resembled the symptoms of Alzheimer's disease.

The drug reversed the disease in the brains of mice who had already developed it. The researchers showed that as zinc and copper were pulled out of the plaques by clioquinol the plaques dissolved.

"So the drug actually hit the target," Bush said. "It seems to profoundly affect beta amyloid metabolism in a way that would be favorable."

When clioquinol was given early enough, it prevented zinc and copper from accumulating in the brains of mice with the Alzheimer's gene and protected them from developing plaques.

"The No. 1 question facing the Alzheimer research community right now is whether limitation of amyloid accumulation will affect the progression of the disease," said Bill Thies, vice president for medical and scientific affairs of the Chicago-based Alzheimer's Association, which helped fund the study.

Prana Biotechnology in Melbourne, Australia, provided major funding and is developing more potent drugs to remove zinc and copper from the brain.

"They have some data that's very encouraging and some data that's not quite so clear," Thies said. "But the fact that they were able to keep people on this medication for 36 weeks and didn't make anybody sick--and there's some suggestion of possible effectiveness--then it justifies a bigger study."

A larger study, expected to start next year, will be directed by Dr. Sam Gandy and Dr. Barry Rovner of the Farber Institute for Neuroscience of Thomas Jefferson University in Philadelphia.

Currently used drugs, such as Aricept, are helpful for some patients. They work by increasing brain levels of acetylcholine, a neurotransmitter necessary for memory. A recently approved drug, Namenda, is designed to protect brain cells from premature death.

An experimental vaccine intended to stimulate the body's immune system to destroy amyloid plaques was halted two years ago because of complications. A new vaccine, expected to be tested soon, will provide patients with ready-made antibodies against plaque.

Clioquinol was taken off the market in 1970 because of possible neurological complications in a small number of patients of Japanese ancestry. Those complications are now attributed to vitamin B12 deficiency, which is easily remedied, Bush said.

The drug does not deplete the body of zinc and copper, Bush said. It appears to work by pulling the two metals out of plaques, which then allows the plaques to dissolve, he said.

In addition to zinc and copper, clioquinol also leeches iron from brain cells, which may be useful in treating Parkinson's disease, Bush said. There is growing evidence that the brains of Parkinson's patients accumulate iron, which produces a toxic reaction that can destroy brain cells, he said.

Mice with a human gene for Parkinson's disease showed significant improvement when treated with clioquinol, Bush said.

Copyright © 2003, Chicago Tribune

Scientist is winning converts on Alzheimer's

By Bernard Wysocki Jr., Associated Press/The Wall Street Journal
BOSTON — Ashley Bush, a 44-year-old researcher at Harvard Medical School, was pilloried after he put forth a radical theory of Alzheimer's disease in 1994.

"Worthless," wrote one scientific critic. Others have described his style as brash, his content as flimsy, and his ideas unworthy of being published. At worst, Bush recalled, it felt like "hate mail."

Over the years, he submitted 30 scientific papers that were rejected by scientific journals. Eight times, his grant applications were spurned by the National Institutes of Health.

Bush's theory is that the real culprit in Alzheimer's is a copper and zinc buildup in the brain — an idea few scientists have looked at. He believes the accumulated metals mix abnormally with a protein called beta amyloid in the brain, oxidizing — literally rusting — and destroying nerve cells. Published in the prestigious journal Science, his hypothesis swiftly drew criticism because it ran counter to the leading theory that Alzheimer's disease is caused mainly by the protein clumps themselves. And by highlighting metals as the culprit, it drew scowls from some who thought it resembled a largely discredited theory that aluminum caused the disease. (He never saw aluminum as a culprit.)

Now scientists are giving Bush more credence. He has a five-year grant from the NIH and this year won an American Academy of Neurology prize for Alzheimer's disease research.

One big reason: He is on the trail of a drug that absorbs his culprits — the excess copper and zinc — and dissolves the protein clumps in the brains of experimental animals. Bush has found a potential Alzheimer's treatment in a 70-year-old dysentery drug with a history of toxic side effects. What's more, he and his colleagues this month published their first human clinical trial showing the drug's promise. "It's like Drano," he says. "It blows them away."

The small trial's results are "significant" and "innovative," says Roger Rosenberg, a neurologist at the University of Texas Southwestern Medical Center and editor of the Archives of Neurology, which published the research.

Bush's odyssey shows how rejects in the world of science can sometimes re-emerge as important figures. The history of science in the last 50 years could be written with papers rejected by prestigious journals, observed Paul Lauterbur of the University of Illinois after he won the 2003 Nobel Prize for medicine. His original paper on his prizewinning achievement, magnetic resonance imaging (MRI), was initially rejected in 1973 by Nature, which later ran it.

It's far from clear whether Bush has unearthed a new key to Alzheimer's that yields a treatment, or just a dry hole. Nobody knows if his drug will work any better than the handful of therapies on the market or the dozens more in the pipeline.

Alzheimer's is a degenerative brain disease, affecting about four million Americans in the U.S. alone. Although not considered part of normal aging, Alzheimer's attacks mostly elderly people. About 1% of those age 65 show symptoms, a rate that surges to nearly 50% by age 85. Its main feature is memory loss, but in advanced stages, the disease erodes personality, judgment, powers of speech and the ability to perform the functions of daily living.

The brains of Alzheimer's victims, when examined at autopsy, appear speckled with two kinds of abnormal protein. One is beta amyloid clumps between brain cells, known as plaques. The other is neurofibrillary tangles, or protein strands that look like knotted skeins of yarn, inside cells. Nobody knows for sure whether these clumps and strands are causes or merely byproducts of the disease. But to many mainstream researchers, the amyloid proteins are the leading suspects.

This is where Bush breaks from the crowd. He believes that amyloid clumps aren't the ultimate villain, but more of an accomplice in the relentless destruction wrought by the disease. "The classic amyloid cascade hypothesis is wrong," he insists.

In Bush's view, amyloid protein plays a helpful role in the brain: absorbing metals like a sponge. But in Alzheimer's victims, he contends, the metals overwhelm the protein. He believes that copper mixes abnormally with amyloid, releasing hydrogen peroxide and other toxic chemicals that damage the nearby cells. Some of that protein breaks free, becomes "rogue" amyloid, and mixes with zinc to form clumps that leak more hydrogen peroxide. Thus he indicts metals as the real culprits. This theory is still controversial.

Some critics see his metals theory as mere speculation. "Based on science, there is no substantiation for what Ashley says," says Bruce Yankner, professor of neurology at Harvard. "Ashley's ideas are interesting. But that's what they are — interesting."

One problem in verifying Bush's hypothesis is the difficulty of measuring copper or zinc in the human brain. Many scientists believe trace amounts of metals exist in the brain, but Bush contends that excessive amounts build up in some aged people. Among unanswered questions is where the metal buildup comes from. Bush doesn't claim to know.

Among Alzheimer's baffling aspects is the fact that it might have multiple causes. A small fraction of the population carries rare mutant forms of certain genes that increase the risk of Alzheimer's. At the same time, many researchers believe that such things as nutrition, exercise and mental stimulation may also play a role in keeping dementia at bay.

In recent years, a handful of drugs have hit the market to treat Alzheimer's, from Pfizer Inc., Johnson & Johnson and other companies, but these offer limited relief. The big challenge is to bring drugs to market that attack the underlying cause of the disease. Because the ultimate cause of Alzheimer's is unknown, different theories have fueled the pursuit of different kinds of drugs. Some aim to prevent the "snipping" of amyloid protein into fragments that form plaques. Bush considers this misguided, since he believes it's the metals interacting with the protein that do the damage.

The son of Jewish refugees from Poland and Palestine who fled their homes for Australia during World War II, Bush grew up in Melbourne. As a medical student at the University of Melbourne, he started training as a surgeon, then switched to psychiatry.

He was drawn to Alzheimer's after working in the mid-1980s as a young physician at a mental institution, where he saw 700 patients with dementia who were given little in the way of diagnosis or treatment. He started studying the possible role of zinc while in Melbourne. He was inspired by a University of Texas researcher, Christopher Frederickson, who detailed the presence of zinc traces in the brain. Bush saw that the zinc and the amyloid were in the exact same spots, giving him a clue that they were somehow inter-related. He stayed on the trail when he moved to Harvard and the affiliated Massachusetts General Hospital in 1992.

Working in the lab of neurologist Rudolph Tanzi, he found that by adding zinc to dead brain tissue in test tubes, the amyloid suddenly formed clumps that looked like Alzheimer's plaques. This was a possible clue that the metals also played a role in triggering the plaques in the living brain as well. Bush submitted the paper to the prestigious journal Science. Tanzi warned he was shooting for the moon. But the paper was published in 1994.

"He started out extremely lucky," says Tanzi, his co-author on this and other papers. More luck followed. He obtained some initial research funding from NIH, and from Prana Biotechnology Ltd., a Melbourne-based biotech he co-founded in 1997.

But Bush's luck soon soured. His work was "bucking conventional wisdom," says Tanzi. He drew attacks from mainstream Alzheimer's researchers who were asked to review his submissions to peer-reviewed journals. One of the reviewers, who are traditionally shielded by anonymity, was especially savage.

"I do not think the manuscript is worthy of being published in Nature or elsewhere," the reviewer wrote, blasting the manuscript as "worthless." Another critic chastised him for muddying the already turbid waters of Alzheimer's research.

By 1999, his frustration rose as grant funds ran low. Like many researchers in academia who lack endowed chairs, Bush isn't paid by Harvard. He runs his lab and pays salaries out of grants and other such funds.

He had hoped a grant from the National Institute on Aging, part of the NIH, would solve his woes. But Tanzi judged some of his protege's proposals as flimsy and ill-crafted. While he admires Bush's originality and experiments, Tanzi says he remains dubious about some of his theories. Bush, he jokes, is considered the "wacky uncle" around the lab.

Meanwhile at closed-door NIH meetings, grant reviewers weren't so jocular. They issued a pointed challenge to his work, Bush recalls. He says these outside experts asked: "If you are so sure this is the cause of Alzheimer's disease, where is your drug?"

"Why am I having such a difficult time?" Bush recalls asking NIH after his rejections.

But it turned out that Bush had an ally at NIH. He was Stephen Snyder, a Ph.D. in pathology at the National Institute on Aging. Snyder oversees grant applications dealing with the origins of Alzheimer's. He heard reviewers complain because Bush's applications were long on brain chemistry and short on biology. Snyder passed all this along to Bush, and vowed to help Bush improve his applications.

It also turned out that Bush was indeed pursuing a treatment. Working with mice given a gene for Alzheimer's, Bush tested oral doses of a 70-year-old drug called clioquinol, versus placebos. When Snyder learned of this, he quickly asked to see the data. After nine weeks, the treated mice had a 49% reduction of beta amyloid deposits.

"Holy Finoki!" Bush e-mailed Tanzi.

In late 1999, Bush sent a photographic slide of the results to the aging institute. Snyder remembers thinking, " 'Wow. This doesn't come along every day.' The placebo mice had huge plaques. The treated mice had brains as clear as the day they were born." He recalls deciding, "I'm going to go to the wall for this."

Bush crafted his ninth NIH grant proposal. The review committee gave it a score in the top third — not great, but enough to get a $750,000, five-year grant.

"The mice came along at the right time," Snyder says. The journal Neuron published the mouse study. In Melbourne, Prana, the biotech company Bush co-founded, prepared to launch human clinical trials.

But there was a problem: Clioquinol had a disastrous history. It was introduced in the 1930s by Swiss drug giant Ciba-Geigy AG, as a treatment for amoebic dysentery, a potentially deadly intestinal ailment. The drug was later promoted in Japan for all types of stomach trouble. By 1970, however, nearly 10,000 people who had been treated with the drug, mostly in Japan, developed paralysis or blindness.

These days, some scientists believe the adverse effects might have been influenced by a vitamin B-12 deficiency in the postwar Japanese diet. So Prana added vitamin B-12 supplements to the clioquinol in the Alzheimer's study. That did the trick, the company says.

Prana's randomized double-blind clinical trial was launched in 2000 and completed by 32 volunteers in 2002. Half of them got clioquinol; half got a placebo. In spring of 2002, Colin Masters, chairman of Prana's scientific board, gave the first peek at the results, declaring Alzheimer's disease was slowed by the drug.

This month the Archives of Neurology published the full report. The results: Volunteers on placebo showed a "substantial worsening" of the disease based upon cognitive tests, while people on clioquinol experienced "minimal deterioration." In addition, blood levels of beta amyloid protein in the blood declined among those taking the drug but increased in those on placebo. As for side effects, the drug was "well-tolerated," wrote Bush and his co-authors from the U.S., Europe and Australia. One participant, who had a history of hypertension and glaucoma, suffered impaired vision during the trial. But the symptoms disappeared when the trial ended.

Now scientists in the U.K,. Japan and the U.S. are pushing forward with research on clioquinol or drugs like it. Doctors at Duke and Thomas Jefferson Universities are planning large-scale clinical trials. There are some glitches. Prana is in a patent dispute with onetime collaborators at a Greek pharmaceutical company, PN Gerolymatos SA. (It didn't respond to requests for comment.) Meantime, Prana is working on a drug similar to clioquinol.

In retrospect, Bush concedes he was treated fairly by the NIH. "I just chose to pursue a subject that defied fashion," he says. "A good scientist needs a thick skin and an irrational sense of optimism."

Copyright 2003 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
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Unfortunately, the drug is contraindicated for children

Because clioquinol is neurotoxic, it was not recommended for children.  This conclusion was made because the condition cliquinal was used for -- treating dermatitis-- was not worth the risk, especially when other drugs were available for the condition.  However, is the risk worthwhile for a condition as severe as autism?

Clioquinol (Iodochlorhydroxyquin, Vioform) and Iodoquinol (Diiodohydroxyquin): Blindness and Neuropathy (RE9198)