Posted on 10/09/2013 9:28:25 PM PDT by neverdem
SCIENTISTS have hailed a historic "turning point" in the search for a medicine that could beat Alzheimer's disease, after a drug-like compound was used to halt brain cell death in mice for the first time.
Although the prospect of a pill for Alzheimer's remains a long way off, the landmark British study provides a major new pathway for future drug treatments.
The compound works by blocking a faulty signal in brains affected by neurodegenerative diseases. The signal shuts down the production of essential proteins, leading to brain cells being unprotected and dying off.
The compound was tested in mice with prion disease - the best animal equivalent of human neurodegenerative disorders - and human clinical trials could take between five and 10 years. But scientists said they were confident the same principles would apply in humans with debilitating brain diseases such as Alzheimer's or Parkinson's.
The study, published today in the journal Science Translational Medicine, was carried out at the Medical Research Council's (MRC) Toxicology Unit at the University of Leicester.
"It's a real step forward," team leader Professor Giovanna Mallucci said.
"It's the first time a substance has been given to mice that prevents brain disease. The fact that this is a compound that can be given orally, that gets into the brain and prevents brain disease, is a first in itself… We can go forward and develop better molecules and I can't see why preventing this process should only be restricted to mice. I think this probably will translate into other mammalian brains."
In debilitating brain diseases like Alzheimer's, the production of new proteins in the brain is shut down by a build-up of "misfolded proteins" or amyloids. This build-up leads to an "over-activation" of a natural defence mechanism that stops essential proteins being produced. Without these proteins to protect them, brain cells die off - leading to the symptoms of diseases like Alzheimer's.
The compound used in the study works by inhibiting an enzyme, known as PERK, which plays a key role in activating this defence mechanism. In mice with prion disease, it restored proteins to protect brain cells "stopping the disease in its tracks", restoring some normal behaviours and preventing memory loss.
Although the compound also produced significant side-effects in mice - including weight loss and mild diabetes - Professor Mallucci said it would "not be impossible" to develop a drug that protected the brain without the side-effects and that work towards doing so had been "very promising".
The breakthrough was greeted with excitement by scientists, who said that while it is not a guarantee of an Alzheimer's cure in the near future, it remains a significant proof of principle.
Professor Roger Morris, acting head of King's College London's department of chemistry, believed the finding "will be judged by history as a turning point in the search for medicines to control and prevent Alzheimer's disease".
"This is the first convincing report that a small drug, of the type most conveniently turned into medicines, stops the progressive death of neurons in the brain as found, for instance, in Alzheimer's disease," he said.
"True, this study has been done in mice, not man; and it is prion disease, not Alzheimer's, that has been cured.
However, there is considerable evidence that the way neurons die in both diseases is similar; and lessons learned in mice from prion disease have proved accurate guides to attenuate the progress of Alzheimer's disease in patients.
"From finding the first effective drug in a mouse, to having an effective medicine in man usually takes decades to bring to fruition… So, a cure for Alzheimer's is not just around the corner. However, the critical point of principle made by… [the] study is that a drug… can arrest neurodegeneration caused by amyloid in the brain."
David Allsopp, professor of neuroscience at Lancaster University, said the study had thrown up "very dramatic and highly encouraging results", but said that more research was needed to overcome the "problematic side-effects" and to prove the technique would be effective against other diseases like Alzheimer's and Parkinson's.
There are currently 800,000 people in the UK with dementia and Alzheimer's disease is the most common cause.
Dr Eric Karran, director of research at Alzheimer's Research UK, said: "What is true in animals does not always hold true in people and the ultimate test for this compound will be to see whether it is safe and effective in people with these diseases."
Read and Weep. http://www.forbes.com/sites/natesadeghi/2012/08/07/the-lessons-of-failure-what-we-can-learn-from-bapineuzumabs-blowup/
If it works in mice now, why is it a long way off for Alzheimer’s victims?
I wouldn’t get my hopes up yet.
The primary side effect is that rather than dying brain cells continue to live and new brain cells grow resulting in the brain issuing through an ear canal
I agree, there is no reason to with hold the drugs or other treatments to terminally ill, as long as they sign waivers of liability.
Great info. Thanks much.
Here's the abstract that's linked in comment# 1.
During prion disease, an increase in misfolded prion protein (PrP) generated by prion replication leads to sustained overactivation of the branch of the unfolded protein response (UPR) that controls the initiation of protein synthesis. This results in persistent repression of translation, resulting in the loss of critical proteins that leads to synaptic failure and neuronal death. We have previously reported that localized genetic manipulation of this pathway rescues shutdown of translation and prevents neurodegeneration in a mouse model of prion disease, suggesting that pharmacological inhibition of this pathway might be of therapeutic benefit. We show that oral treatment with a specific inhibitor of the kinase PERK (protein kinase RNA–like endoplasmic reticulum kinase), a key mediator of this UPR pathway, prevented UPR-mediated translational repression and abrogated development of clinical prion disease in mice, with neuroprotection observed throughout the mouse brain. This was the case for animals treated both at the preclinical stage and also later in disease when behavioral signs had emerged. Critically, the compound acts downstream and independently of the primary pathogenic process of prion replication and is effective despite continuing accumulation of misfolded PrP. These data suggest that PERK, and other members of this pathway, may be new therapeutic targets for developing drugs against prion disease or other neurodegenerative diseases where the UPR has been implicated.
Hey Neverdem,
Nothing wrong in your posting this material. I had alreaday looked at this abstract. I find the conclusions by the authors to be flawed and misleading.
I’m not weeping, I don’t have a dog in this fight.
Just interested in medicine and biology in general.
Actually you have millions of dogs in this fight. Alzheimer’s and obesity are the same pathology. We have lost the obesity battle so far. The useful idiots in main stream media dribble out a perpetual stream of slobber like this publication in order to confuse and anesthetize the public.
Thanks for the ping.
Just received this today.
http://www.futurity.org/can-peanut-butter-smell-test-confirm-alzheimers/
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.