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Alzheimer’s breakthrough from University of Cambridge scientists ‘could lead to drug trials in two years’

Scientists in Cambridge and Sweden have unveiled a world first in the battle against Alzheimer’s disease, which could lead to trials of new drugs in two years. They have developed a new way to target the toxic particles that are now agreed to be the underlying cause of the disease.
Professor Sir Christopher Dobson, master of St John's College, Cambridge. Picture: Keith HeppellProfessor Sir Christopher Dobson, master of St John’s College, Cambridge. Picture: Keith Heppell

Scientists in Cambridge and Sweden have unveiled a world first in the battle against Alzheimer’s disease, which could lead to trials of new drugs in two years. They have developed a new way to target the toxic particles that are now agreed to be the underlying cause of the disease.

The method developed at the University of Cambridge and at Lund University will enable a new approach to developing dementia drugs.

Professor Michele Vendruscolo, from Cambridge’s Department of Chemistry, said: “This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease – has been proposed.

From left, Professor Tuomas Knowles, Professor Sir Christopher Dobson and Professor Michele Vendruscolo. Picture: Keith HeppellFrom left, Professor Tuomas Knowles, Professor Sir Christopher Dobson and Professor Michele Vendruscolo. Picture: Keith Heppell

“Until very recently scientists couldn’t agree on what the cause was so we didn’t have a target. As the pathogens have now been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to aim drugs at these toxic particles.”

Alzheimer’s is the leading cause of dementia. Across the UK, about 850,000 people are believed to be living with dementia – a number expected to rise to more than one million by 2025. The risk increases with age, with about one in 14 people over the age of 65 and one in every six people over the age of 80 affected by dementia.

Alzheimer’s causes the death of nerve cells and tissue loss in the brain, leading to it shrinking dramatically over time. The destruction leads to memory loss, personality changes, and challenges in carrying out everyday activities.

Abnormal deposits called protein oligomers are now seen as the likely culprit of dementia. These rogue proteins form clumps in the brain, killing healthy neurons.

“A healthy brain has a quality control system that effectively disposes of potentially dangerous masses of proteins, known as aggregates,” said Prof Vendruscolo, who is the lead author of the paper published in the journal PNAS.

“As we age, the brain becomes less able to get rid of the dangerous deposits, leading to disease.

“It is like a household recycling system, if you have an efficient system in place then the clutter gets disposed of in a timely manner. If not, over time, you slowly but steadily accumulate junk that you don’t need. It is the same in the brain.

“Our research is based on the major conceptual step of identifying protein oligomers as the pathogens and reports a method to systematically develop compounds to target them. This approach enables a new drug discovery strategy.”

The international research team also included Professor Sir Christopher Dobson, master of St John’s College, who co-founded the Centre for Misfolding Diseases (CMD).

“This interdisciplinary study shows that it is possible not just to find compounds that target the toxic oligomers that give rise to neurodegenerative disorders but also to increase their potency in a rational manner,” he said.

“It now makes it possible to design molecules that have specific effects on the various stages of disorders such as Alzheimer’s disease, and hopefully to convert them into drugs that can be used in a clinical environment.”

The team is hopeful that their first drug candidates could reach clinical trials in as little as two years.

They have co-founded biotechnology company Wren Therapeutics in the Chemistry of Health building in Cambridge, which opened last Friday. Its mission is to translate the university’s research into new methods of diagnosis and treatment for Alzheimer’s and other misfolding disorders.

Although there have been about 400 clinical trials for Alzheimer’s drugs, none has yet specifically targeted the pathogens that cause it.

The team’s approach is based on chemical kinetics developed over a decade by scientists led jointly by Prof Tuomas Knowles, also a fellow at St John’s College, Prof Dobson and Prof Vendruscolo, working at the new centre in Cambridge, in collaboration with scientists at Lund University, led by Prof Sara Linse.

Prof Knowles said: “Since the process of aggregation is highly dynamic, the framework of kinetics allows us to approach this problem in a new way and find approaches to stop the generation of toxic proteins species at their very source.”

Dr David Reynolds, chief scientific officer from Alzheimer’s Research UK, also based in Cambridge, told the Cambridge Independent: “This study outlines an interesting approach for targeting what are thought to be key molecular culprits in Alzheimer’s disease.

“There is still a lot of work needed to generate molecules that could form the basis of new drugs, therefore it is difficult to predict how long it could take for these findings to lead to medications that could be tested in clinical trials.”

Dementia is the only condition in the top 10 causes of death in the UK without a treatment to prevent, cure or slow its progression.


Source:

http://www.cambridgeindependent.co.uk

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