A new approach to creating drugs to treat Alzheimer’s disease, which has identified two potential new therapies, has been developed by a pioneering team of scientists from the University of Sheffield.
The new drug leads are able to target the three pillars that cause Alzheimer’s disease, and improve on previous approaches to developing new treatments for the debilitating disease.
Professor Beining Chen, from the University of Sheffield, said: "Despite recent clinical trials there have been no successful drug leads which target all three key players that cause this complex disease.
"Our project was aimed at tackling the tough challenges in drug discovery and this is our first breakthrough in using a multi-targeted approach to identify new leads against a disease like Alzheimer’s."
The professor of medicinal chemistry added: "Not only have we developed a new approach to creating treatments for Alzheimer’s, we have identified two new drug leads."
Alzheimer’s, also known as Alzheimer’s disease dementia, affects about 850,000 people in the UK, while 50 million people are thought to be living with the disease globally.
The disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks.
As we live longer, all forms of dementia are increasing. Alzheimer’s disease is the most common form of dementia, responsible for 80 per cent of cases, and is predicted to affect 150 million people worldwide in less than 30 years.
The causes of the disease are complex, but it is known that two rogue versions of natural proteins are involved.
The first, called beta amyloid (Aβ), triggers the formation of plaque around brain cells, preventing them from communicating properly. While the second, called Tau, forms toxic tangles inside the brain cell which stops it from transporting essential nutrients.
These two events are connected and scientists believe a third molecule, called PrPᶜ, is responsible as when it binds to the rogue Aβ it leads to the distinctive cognitive impairment and neurotoxicity seen in Alzheimer’s disease.
Together, Aβ, Tau and PrPᶜ are seen as the three pillars which cause Alzheimer’s disease. Yet, most recent drug trials for Alzeimer’s disease have only targeted Aβ, by trying to prevent it causing plaques and inducing Tau to start tangling. This approach has so far proved to be unsuccessful.
The Sheffield university team has identified two new drug leads that not only bind to Aβ, but block its interaction with PrPᶜ and disrupts the formation of Tau tangles.
Professor Chen said: "We are very pleased that this collective effort which has involved multiple academic and industrial partners has been so successful.”
As part of the research the team used computer programs to search through thousands of molecules to identify promising drug leads.
These then went through a combination of test tube experiments to find which compounds bound Aβ best, leading to six lead candidates that were then tested in stem-cell models.
For the future the team now hopes to gain funding to further their research by using these new compounds in drug candidates for pre-clinical and clinical studies.
People who have suffered from Alzheimer's disease include the Carry On and EastEnders actress Dame Barbara Windsor who was diagnosed with Alzheimer's disease in 2014, and passed away in December last year aged 83, after her condition worsened.
Dame Barbara, who appeared in nine Carry On films and played the pub landlord Peggy Mitchell in EastEnders, did not go public with the news until 2018.
The veteran of film and TV, and her husband Scott Mitchell have campaigned to raise awareness of dementia, which is most common in people over the age of 65.
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