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Human study: Clioquinol stops Alzheimer's disease

Hua Kul gmp at adres.nl
Mon Jan 12 20:55:30 EST 2004

(The following is from the thread

> Tim Tyler (tim at tt1.org)
> Subject: Re: Copper & Alzheimer's Disease 

> A report of a previous study:

> ``Research teams at Harvard Medical School, the University of Melbourne,
>   and Prana Biotechnology Ltd in Australia are working collaboratively on
>   giving Alzheimer's-prone mice copper chelators, substances that sop up
>   metals and eliminate them from the body. These new metal-binding drugs
>   effectively "melted" the amyloid plaques in living mice in as little as
>   nine weeks, and are now in clinical trials with Alzheimer's
>   patients. Results of the first of these drugs, clioquinol, should be
>   known within 12 months, and further trials of this approach are
>   currently in preparation.''

>  - http://www.infoaging.org/d-alz-9-r-metals.html
> -- 
>  |im |yler  http://timtyler.org/  tim at tt1.org

Here is a small study indicating clioquinol virtually halted
progression of moderate AD in humans.

1: Arch Neurol. 2003 Dec;60(12):1685-91.  Related Articles, Links  

Comment in: 
Arch Neurol. 2003 Dec;60(12):1678-9.
Metal-protein attenuation with iodochlorhydroxyquin (clioquinol)
targeting Abeta amyloid deposition and toxicity in Alzheimer disease:
a pilot phase 2 clinical trial.

Ritchie CW, Bush AI, Mackinnon A, Macfarlane S, Mastwyk M, MacGregor
L, Kiers L, Cherny R, Li QX, Tammer A, Carrington D, Mavros C,
Volitakis I, Xilinas M, Ames D, Davis S, Beyreuther K, Tanzi RE,
Masters CL.

Departments of Pathology, The University of Melbourne, The Mental
Health Research Institute of Victoria, Parkville, Victoria, Australia.

BACKGROUND: Alzheimer disease (AD) may be caused by the toxic
accumulation of beta-amyloid (Abeta). OBJECTIVE: To test this theory,
we developed a clinical intervention using clioquinol, a
metal-protein-attenuating compound (MPAC) that inhibits zinc and
copper ions from binding to Abeta, thereby promoting Abeta dissolution
and diminishing its toxic properties. METHODS: A pilot phase 2
clinical trial in patients with moderately severe Alzheimer disease.
RESULTS: Thirty-six subjects were randomized. The effect of treatment
was significant in the more severely affected group (baseline
cognitive subscale score of the Alzheimer's Disease Assessment Scale,
>/=25), due to a substantial worsening of scores in those taking
placebo compared with minimal deterioration for the clioquinol group.
Plasma Abeta42 levels declined in the clioquinol group and increased
in the placebo group. Plasma zinc levels rose in the
clioquinol-treated group. The drug was well tolerated. CONCLUSION:
Subject to the usual caveats inherent in studies with small sample
size, this pilot phase 2 study supports further investigation of this
novel treatment strategy using a metal-protein-attenuating compound.

Publication Types: 
Clinical Trial 
Clinical Trial, Phase II 
Randomized Controlled Trial 

PMID: 14676042 [PubMed - indexed for MEDLINE] 



Here'a an article on the study.

Drug used to treat athlete's foot 'slows down Alzheimer's'
By Michael Day and Martyn Halle
(Filed: 11/01/2004) 

A drug that is used in the treatment of athlete's foot could be used
to treat Alzheimer's disease, according to a new study by British

Iris Murdoch, who died in 1999, and her husband John Bayley 
The study, by a team from University College, London, found that
clioquinol, a drug that is also used to treat ear infections and
indigestion, can almost halt the progression of Alzheimer's.

It discovered that clioquinol, which was developed 100 years ago, is
able to absorb the zinc and copper atoms that concentrate in the
brains of Alzheimer's sufferers before dementia sets in.

Doctors believe that by absorbing these atoms, clioquinol can arrest
the onset of dementia, potentially helping thousands of people.

Dr Craig Ritchie, a psychiatrist at UCL and a Medical Research Council
research fellow who led the trial, said that the results were "very

"The patients on this trial had Alzheimer's that was mild to moderate,
but there was very little change in their brains once they had started
treatment," he said.

"This drug could give your mind a chance to stay healthy as long as
your body does. Particularly for patients who get this terrible
disease in middle age, we need better treatments."

The study was prompted by research at Melbourne University in
Australia and Harvard University in the United States, which found
that clioquinol could prevent zinc from building up on the surface of
the brain.

Academics from the universities speculated that by blocking zinc they
could halt, and possibly reduce, the brain damage that causes
Alzheimer's victims to lose their memory.

To test their theory, the UCL doctors tested 13 Alzheimer's patients,
giving them clioquinol over a nine-month period, and 13 other
Alzheimer's sufferers who were given a placebo.

The results, published in the Archives of Neurology, show that
patients given clioquinol retained significantly more mental capacity
than those who received the placebos. Dr Ritchie said that the
patients taking clioquinol experienced a decline in their mental
faculties of just 1.4 per cent.

"You would normally see a drop of four points or more in someone with
Alzheimer's over the period of time we treated these patients," he
added. "For those taking the placebo, their mental decline was 8.9 per
cent. It's a very large gap and indicated that the drug was working."

Alzheimer's affects one in 10 people over the age of 65, and almost
half of those aged 85 and over.

The protective effect of clioquinol appears to be nearly twice as
great as that of the latest generation of Alzheimer's drugs, such as
donepezil, which are expensive and not always widely available.

A survey by Pfizer, the drug company, revealed last week that the
availability of treatments, which cost up to £100 a month, varied
sharply across Britain. In the worst area, Lothian in Scotland, less
than £1 a head was spent on these drugs in the over-65 population
compared with more than £10 a head in Northern Ireland.

Clioquinol should be much cheaper because it is no longer protected by
a patent.

Prana Technology, an Australian drug firm, provided clioquinol for the
first small trial. Larger trials of the drug are expected to start
shortly and will include British patients.

Dr Ritchie said that animal studies had suggested that the drug might
even reverse the progress of the dementia - something that current
treatments are unable to do.

"We know that in mice the disease was reversed. Everyone is excited
but this was only a small trial and we have to do a larger trial. We
think this drug will produce the same results in extended trials with
humans. If we can get to them early, we might be able to treat
patients and leave them with very little damage to their brain."

One fear over the long-term use of clioquinol is that it may damage
peripheral nerves and the nerves in the eye. Dr Ritchie said his team
found no evidence of this during their trial.

Dr Susanne Sorensen, the head of research at the Alzheimer's Society,
said: "The UCL research suggests that there may be a novel use for
this already existing drug in the treatment of Alzheimer's disease.
But the trial is limited in its scale and we believe it would be
valuable to see a larger scale trial.

"The potential for new drugs that may interfere with or revert the
progression of Alzheimer's disease gives hope to people with dementia
and their carers."

The plight of sufferers and their carers was brought home to millions
two years ago when the film biography of the novelist Iris Murdoch was
showered with awards for its touching and realistic portrayal of the
writer's dementia.



--Hua Kul
huaREMOVEkul at hotmail.com

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