A team of scientists at the University of Sheffield have adopted a new method of creating Alzheimer’s drugs, which has identified two potential new treatments for the disease.
Alzheimer’s Disease is the most common form of dementia, accounting for 80% of current cases,and, it is predicted to affect 150 million people around the world, within 30 years.
Through the new approach to Alzheimer’s drugs, a multidisciplinary research team led by scientists at the University of Sheffield, have been able to target three pillars causing Alzheimer’s disease and will be able to improve on the development of new treatments.
There is still a lot left to learn about the complex causes of Alzheimer’s Disease, but it is currently understood that causes involve rogue versions of natural proteins.
The first of these proteins, named beta amyloid (Aβ), prevents brain cells from communicating properly by causing the development of plaque around the cells.
The second protein, Tau, prevents brain cells from transporting essential nutrients by constructing toxic tangles inside the cells.
These two processes are connected, and further, scientists have theorised that a third molecule, PrPᶜ, is a cause, as when it binds to the rogue Aβ, it results in distinctive cognitive impairment and neurotoxicity, seen in patients with Alzheimer’s disease.
Aβ, Tau and PrPᶜ are considered the three pillars that cause Alzheimer’s disease. However, recent Alzheimer’s drug trials have only targeted preventing Aβ from causing plaque formation, inducing Tau to start tangling. Currently, this approach has been unsuccessful.
The team of Sheffield University scientists has identified two drug leads that bind to Aβ, prevent its interaction with PrPᶜ, and disrupt the formation of Tau tangles.
Professor Beining Chen, Professor of Medicinal Chemistry at the University of Sheffield, commented: “Over 50 million people are thought to be living with Alzheimer’s disease, 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 multifactorial disease like Alzheimer’s. Not only have we developed a new approach to creating treatments for Alzheimer’s, but we have identified two new drug leads.
“We are very pleased that this collective effort which has involved multiple academic and industrial partners has been so successful.”
The team used computer programmes to undertake a molecular-sifting process and identify Alzheimer’s drug leads. These leads then went through various test tube experiments to discover which compounds bound Aβ best; this led to six candidates that were tested in stem-cell models. The final tests narrowed the search to two compounds that targeted all three pillars.
Moving forward, the team hopes to gain funding so they can continue their research by optimising the compounds into drug candidates for pre-clinical and clinical studies.
