IUBio

Human study: Clioquinol stops Alzheimer's disease

k p Collins kpaulc at [----------]earthlink.net
Mon Jan 12 21:58:43 EST 2004


If one takes action that indiscriminantly 'blocks' the
normal functions of zinc and copper ions, then one
is blocking more than the roles that these ions play
in the formation of 'plaques'.

In my view, Alsheimer's results from larger dynamics
in which the 3-D energydynamics that 'normally'
focus selective addressing of the DNA-RNA are
prematurely terminated, yielding incompletely-
formed 'protein'-scraps that are what the "plaques"
are.

This's a classic instance of 'inability' to achieve
sufficient TD E/I-minimization in which molecular-
'level' 3-D energydynamics are prematurely-
terminated be-cause TD E/I-minimization does
not procede to 'completion' - it's a "pawling" [AoK,
Ap5]deficit within the TD E/I-minimization mech-
anisms as they are discussed in AoK.

The treatment that will work will re-establish the
normal DNA-RNA-tuning durations by re-establish-
ing the 'normal' functional-scopes of TD E/I-mini-
mization.

Look for the "pawling" deficit, and its causes.

Blanket-blocking of this or that ion's action will
not work.

k. p. collins

"Hua Kul" <gmp at adres.nl> wrote in message
news:3da4c6e5.0401121755.7cecf1af at posting.google.com...
> (The following is from the thread
>
http://groups.google.com/groups?hl=en&lr=&ie=UTF-8&oe=UTF-8&threadm=afe2faf1
.0308141829.d00f6d2%40posting.google.com&rnum=2&prev=/groups%3Fhl%3Den%26lr%
3D%26ie%3DUTF-8%26oe%3DUTF-8%26q%3Dclioquinol%26btnG%3DGoogle%2BSearch%26met
a%3Dgroup%253Dsci.life-extension)
>
> > 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]
>
>
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=14676042&dopt=Abstract
>
> ======================================================================
>
> 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
> doctors.
>
>
> 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
> exciting".
>
> "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.
>
>
http://news.telegraph.co.uk/news/main.jhtml?xml=/news/2004/01/11/nalz11.xml&
sSheet=/news/2004/01/11/ixhome.html/news/2004/01/11/nalz11.xml
>
> =====================================================================
>
>
> --Hua Kul
> huaREMOVEkul at hotmail.com





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