Scientists have claimed a major breakthrough in the hunt for a miracle Alzheimer’s drug after mapping the molecular changes which cause the illness for the first time.
For the last 15 years experts have known that the state of dementia is caused by neurons in the brain being killed off by a faulty protein.
But they have been unable to tell how the harmful part of the Amyloid Beta (ABeta) peptide protein is formed.
A team of Cambridge University scientists have now traced the series of chemical changes which create the neuron-killing chemical.
They are hailing the discovery as an historic landmark in the quest for an Alzheimer’s drug because for the first time scientists can see which processes they must “block”.
Chemists say they now know “the face of their enemy” – and a preventative drug could be developed within the next five-ten years.
The new chemical ‘map’ is also expected to help with earlier diagnosis of Alzheimer’s and prove significant in treating other neurological disorders, including Parkinson’s Disease.
Dr. Tuomas Knowles, who is leading the Cambridge research, described the findings as ‘game-changing’.
He said: “We all have the ABeta protein in our brains. The ABeta protein is supposed to be unfolded.
“When it folds in an inappropriate manner it creates small clumps – called plaques and oligomers.
“The plaques’ size and density renders them insoluble, and consequently they are unable to move.
“But the oligomers are small enough to spread easily around the brain.
“We knew that oligomers go on and interact with neurons in the brain in inappropriate ways.
“They cause the neurons to die which gives the symptoms of Alzheimer’s Disease.
“But although we knew the oligomers were present in the killing of neurons and that they are toxic, we didn’t know how they were formed.
“Now we have mapped the molecular pathway of how the oligomers are formed we can develop treatments to halt that process.
“The most effective treatment for Alzheimer’s would target the first stage of the pathway – that is the best time to intervene.
“I would guess it will take at least five or ten years for a drug to be developed. Identifying the molecular pathway is the first stage in developing a drug.
“The pathway gives us a target making it possible to do rational drug design.”
He added: “We now know the face of the enemy. If you do not know the pathway of how something is formed you are working blind.
“With a disease like Alzheimer’s, you have to intervene in a highly specific manner to prevent the formation of the toxic agents.
“Now we’ve found how the oligomers are created, we know what process we need to turn off.
“This breakthrough is really exciting. What we have discovered is how people have made progress in developing cures for other diseases.
“It is fantastic to draw attention to one of the biggest concerns of the national heath system – how to treat neurological disorders. This is a milestone.”
Diseases like Alzheimer’s are caused by a neurodegenerative process triggered when normal structures of protein molecules within cells become corrupted.
The ‘malfunction’, or ‘misfolding’ proteins were first identified by Cambridge University professor Christopher Dobson 15 years ago.
Protein molecules are made in cellular ‘assembly lines’ that join together chemical building blocks called amino acids in an order encoded in DNA.
New proteins emerge as long, thin chains that normally need to be folded into compact and intricate structures to carry out their biological function.
But Prof Dobson found under some conditions proteins can ‘misfold’ and snag surrounding normal proteins.
They can then tangle and stick together in clumps which build to masses, frequently millions, of malfunctioning molecules that shape themselves into unwieldy protein tendrils.
The abnormal tendril structures, called ‘amyloid fibrils’, grow outwards around the location where the focal point, or ‘nucleation’ of these abnormal “species” occurs.
Amyloid fibrils can form the foundations of huge protein deposits – or plaques – long-seen in the brains of Alzheimer’s sufferers.
These plaques were previously believed to be the cause of Alzheimer’s before the discovery of ‘toxic oligomers’ by Prof Dobson and others a decade or so ago.
It is these oligomers, which give rise to Alzheimer’s disease, which are small enough to spread easily around the brain – killing neurons and interacting harmfully with other molecule.
Researchers now know the way to prevent Alzheimer’s is by designing a drug which halts the first chemical changes which create these oligomers.
In 2010, the Alzheimer’s Research Trust showed that dementia costs the UK economy over #23 billion – more than cancer and heart disease combined.
The breakthrough comes just a week after Prime Minister David Cameron urged scientists and clinicians to work together to “improve treatments and find scientific breakthroughs” to address “one of the biggest social and healthcare challenges we face.”
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said: “Understanding the molecular changes that take place in the brain during Alzheimer’s is important because it provides targets for the development of new treatments to stop the damage.
“Treatments targeting the build-up of amyloid are already in development and these findings could help to refine the design of future treatments.
“As with every potential new drug, studies in humans will provide the ultimate test of their success.”
The Cambridge research was published on Monday in the journal PNAS.
