Amyloid blockers may be a dead end

With few approved drugs available to treat Alzheimer disease, researchers are working on new compounds that block amyloid formation. But many potential drugs in the pipeline for the disease and other amyloid-associated illnesses may not be as promising as thought, according to a new linkurl:study;http://www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.65.html published today (January 27) in Nature Chemical Biology. The research, led by linkurl:Brian Shoichet;http://ucsf.edu/dbps/facu

By | January 27, 2008

With few approved drugs available to treat Alzheimer disease, researchers are working on new compounds that block amyloid formation. But many potential drugs in the pipeline for the disease and other amyloid-associated illnesses may not be as promising as thought, according to a new linkurl:study;http://www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.65.html published today (January 27) in Nature Chemical Biology. The research, led by linkurl:Brian Shoichet;http://ucsf.edu/dbps/faculty/pages/shoichet.html at the University of California, San Francisco, examined the action of eight compounds that are known to inhibit protein aggregation and linkurl:amyloid formation; -- some of which are in early stage testing as therapies. Using electron microscopy, the group demonstrated that the compounds do block linkurl:amyloid formation;http://www.the-scientist.com/2007/11/1/78/2/, but inhibit linkurl:other proteins;http://www.the-scientist.com/templates/trackable/display/news.jsp?type=news&o_url=news/display/24841&id=24841 as well. "It strongly suggests that a lot of leads for drug discovery that people have been pursuing for protein aggregation diseases are probably artifacts," Shoichet told The Scientist. The fact that these compounds are not specific and block any protein they come in contact with suggests that "these inhibitors are probably the wrong direction" for drug discovery, Shoichet added. "It's a very important beginning for uncovering therapeutics that can affect these diseases," linkurl:Colin Masters,;http://www.mdhs.unimelb.edu.au/aboutus/staff an Alzheimer researcher at the University of Melbourne, who was not involved in the study, told The Scientist. Master's team has been working with one of the molecules that Shoichet's group tested, clioquinol, and said that this study will help elucidate some unusual inhibiting activity data that Master's group has been trying to reconcile.
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Comments

Avatar of: Sergio Stagnaro

Sergio Stagnaro

Posts: 59

January 28, 2008

In my web resources (http://www.semeioticabiofisica.it) I describe an original biophysical-semeiotic method that is easy to apply at the bed side. This method is also reliable in recognizing Alzheimer's Disease, even in initial and/or symptomless stage (See an appropriate document at the application page of my web site). In such neurodegenerative disorder, in my opinion, we must aim early ?clinical? diagnosis, possibly soon after the disease on-set, or better in the so-called ?pre-pathological? phase (i.e. at the disease ?real? risk). The diagnosis must be necessarily ?clinical?, and GPs (whom these patients visit first) have to recognize the initial or ?pre-pathological? stages. These stages are characterized functionally by modification of Neuronal and Cerebral Evoked Potentials, and nowadays can be assessed at the bed-side by means of Biophysical Semeiotics (see Cerebral Tumour application of the method at http://www.semeioticabiofisica.it). In healthy, from the microcirculatory point of view, during stress test both vasomotility (chaotic-deterministic oscillations of cerebral arterioles) and vasomotion (chaotic-deterministic fluctuations of nutritional capillaries and post-capillary venules) particularly in hippocampus, pre-frontal and parietal cerebral regions are maximally activated. On the contrary, individuals with a family history positive for Alzheimer?s disease (and, of course, in patients in the first stages of the disease) under identical conditions have a particular form of microcirculatory activation, characterized by increased vasomotility and decreased vasomotion. I termed this condition "dissociated type". In brief, the flow- and flux-motion in the cerebral microcirculatory bed appears to be clearly decreased, possible due to the dangerous phenomenon of the so-called "microcirculatory blood-flow centralization". I hope that sucha as clinical method could suggest also a new way in the treatment.
Avatar of: null null

null null

Posts: 11

January 28, 2008

The public and the government need to realize and refute the hypothesis that amyloid proteins are the cause of Alzheimer's Disease, which has been proven to be false, again and again, but persistently used as a great hoax by those who benefit financially and professionally. The Amyloid Hypothesis is nothing less than a huge medical fraud - pure and simple.
Avatar of: anonymous poster

anonymous poster

Posts: 1

January 28, 2008

To null null-\n\nIf it has been proven "again and again" that amyloid does not cause Alzheimer's disease please kindly provide the evidence to back up your statements.
Avatar of: null null

null null

Posts: 11

January 29, 2008

Please refer to "Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses." by Lee et al. (2007) for a recent repudiation to the Amyloid Hypothesis. Here's the NCBI link to the article.\n\nhttp://www.ncbi.nlm.nih.gov/pubmed/17229880?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum \n\nLikewise, can you provide any article which proves that amyloids cause AD? I think not.
Avatar of: Aaron McCoy

Aaron McCoy

Posts: 1

January 30, 2008

amyloid polymers may or may not cause symptoms in alz. patients but you can bet your last grant check that you will find them in the brain and spinal fluid of postmortem ad victims. i have seen some beautiful atomic force microscopy images from researchers at my alma mater.

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