By Kate Kelland, Reuters May. 06, 2012 10:01AM PDT
LONDON (Reuters) - Scientists have figured out how to stop brain cell death in mice with brain disease and say their discovery deepens understanding of the mechanisms of human neurodegenerative diseases such as Alzheimer's and Parkinson's.
British researchers writing in the journal Nature said they had found a major pathway leading to brain cell death in mice with prion disease, the mouse equivalent of Creutzfeld-Jacob Disease (CJD).
They then worked out how to block it, and were able to prevent brain cells from dying, helping the mice live longer.
The finding, described by one expert as "a major breakthrough in understanding what kills neurons", points to a common mechanism by which brain diseases such as Alzheimer's, Parkinson's and CJD damage the nerve cells.
In neurodegenerative diseases, proteins "mis-fold" in a various ways, leading to a buildup of misshapen proteins, the researchers explained in the study.
These misshapen proteins form the plaques found in the brains of patients with Alzheimer's and the Lewy bodies found in Parkinson's disease.
"What's exciting is the emergence of a common mechanism of brain cell death, across a range of different neurodegenerative disorders, activated by the different mis-folded proteins in each disease," said Giovanna Mallucci, who led the research at the University of Leicester's toxicology unit.
"The fact that in mice with prion disease we were able to manipulate this mechanism and protect the brain cells means we may have a way forward in how we treat other disorders," she said in a statement about the work.
An estimated 18 million people worldwide suffer from Alzheimer's, and Parkinson's is thought to affect around one in 100 people over the age of 60. In these diseases, neurons in the brain die, destroying the brain from the inside.
But why the neurons die has remained an unsolved mystery, presenting an obstacle to developing effective treatments and to being able to diagnose the illnesses at early stages when medicines might work better.
Mallucci's team found that the buildup of mis-folded proteins in the brains of mice with prion disease activated a natural defense mechanism in cells, which switches off the production of new proteins.
This would normally switch back on again, the researchers explained, but in these ill mice the continued build-up of misshapen proteins keeps the switch turned off. This is the trigger point leading to brain cell death, because key proteins essential for cell survival are not made.
By injecting a protein that blocks the "off" switch, the scientists were able to restore the production of the survival proteins and halt the neurodegeneration.
They found the brain cells were protected, protein levels were restored and synaptic transmission - the way brain cells signal to each other - was re-established. The mice also lived longer, even though only a very small part of their brains had been treated.
Eric Karran, director of research at the charity Alzheimer's Research UK, said while the research was still at an early stage, the results were exciting.
"While neurodegenerative diseases can have many different triggers, this study suggests that they may act through a common mechanism to damage nerve cells. The findings present the appealing concept that one treatment could have benefits for a range of different diseases," he said.
Roger Morris, a professor of molecular neurobiology at King's College London who was not involved in the work, said the finding was "a major breakthrough in understanding what kills neurons in neurodegenerative disease".
1 - This article illustrates how much remains to be learned about degenerative brain diseases.
2 - This article illustrates that PBT2, by itself, may not be the only way to treat such diseases, and it is probably not a "magic bullet".
3 - This article illustrates the possibility of using a dual approach to treating such diseases: Use an MPAC compound to restore and maintain proper metals homeostasis, in combination with using the approach described in the article to prevent cell death.
I do not think it illustrates how much remains to be lerned about degenerative brain diseases. It's target was totally very different than to measure knowledge. It produced only one small piece of it. But it is a a paper among thousands of other papers and the value of it will be very big or very small, who knows. Every month there are already hundreds of papers about neurodegeneration and this is one of them.
It does not illustrate anything about PBT2 but it illustrates that misfolding of a protein (what is already known) is one step in neurodegeneration and also something more about cell death. Even from the works of Susan Lindquist (December 2011) we already know that PBT2 prevents this misfolding to happen. Different MPACs in Prana's portfolio have similar effects in these deurodegenerative disease, preventing misfolding, demonstrated by Linquist. A couple of days ago I posted a study demonstrating how the metals on atomistic level cause misfolding.
This paper does not give any "dual approach" possibility about MPAC and something else to prevent cell death. It is already known that PBT2 prevents cell death ( many papers, an example the mouse study over 1 y ago), but PBT2 treatment also demonstrated regrowth of the neural structures. It is much more than just explaining cell death as was done in this study. But best of all PBT2 did not only prevent the death of neurons in the brain but improved cognition. That means that the neurons started to work as they had been doing before the degenerative process. It would be wonderful if one day there would be a new compound which would improve the effect of PBT2 but I do not think this article has nothing to with improving the cognition improving effect of PBT2.
However it is an interesting paper and published in a top journal. It may one day be much more than what I can value it today from the point of Prana investor. This is only my opinion.
To put that into perspective, Prana have turned the disease in HUMANS. Ever seen a mouse reading a book. The brains are quite different. PBT2 is going in before the trigger to restor neuron health before the nasty cascade begins. Whats even more impressive is that Prana's PBT appears to stop the advance of the disease, even after it has begun, as well, IN HUMANS.