SHEFFIELD, United Kingdom — A new treatment for Alzheimer’s disease could be on the horizon thanks to a major scientific breakthrough. Scientists from the University of Sheffield have discovered two new compounds which could help develop new drugs to treat the memory destroying disease.
Unlike existing Alzheimer’s treatments, the promising new drug leads can target the three pillars that cause cognitive decline in patients. These are the formation of plaques, tangles forming in brain cells, and a specific molecule binding to the brain. The new approach has identified two potential new therapies for dementia, but it may also treat other diseases with complex causes like cancer.
“Over 50 million people are thought to be living with Alzheimer’s disease,” says Professor of Medicinal Chemistry Beining Chen in a university release. “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, 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,” Prof. Chen continues.
Pinning down the cause of Alzheimer’s disease
As we live longer, the risk for all forms of dementia increase. Alzheimer’s is the most common form of dementia, responsible for 80 percent of all cases. The World Health Organization predicts the cognitive condition will affect over 150 million people worldwide in less than 30 years.
The Sheffield team is developing a new approach to creating drugs to treat Alzheimer’s; leading to the discovery of these two potential therapies. The new drug leads can target multiple pathways involved in the development of Alzheimer’s. They also improve on previous approaches to developing new treatments for the debilitating disease.
Prof. Chen explains that Alzheimer’s complex origins revolve around two rogue versions of natural proteins in the brain. The first, beta amyloid (Aβ), can trigger the formation of plaque around brain cells. This prevents neurons from communicating properly.
The second, Tau proteins, form toxic tangles inside the brain cells which stops them from transporting essential nutrients. These two events are connected and scientists believe a third molecule, PrPᶜ, is responsible.
This is because when PrPᶜ binds to the rogue beta amyloid, it leads to the distinctive cognitive impairment and neurotoxicity typical in Alzheimer’s disease. Together, beta amyloid, Tau, and PrPᶜ form the three pillars which scientists now believe causes brain function to deteriorate.
Closing in on a cure?
Until now, most recent drug trials for Alzheimer’s Disease have only targeted beta amyloid. These treatments try to prevent the protein from causing plaques and inducing Tau to start tangling. This approach has so far proved to be unsuccessful.
The new study identified that the two new drug leads not only bind to beta amyloid, but also block its interaction with PrPᶜ — disrupting the formation of Tau tangles. Researchers discovered these compounds through a complex molecular-sifting process.
Scientists began by using computer programs to search through thousands of molecules to identify promising drug leads. Next, these went through a combination of test tube experiments to find which compounds bound beta amyloid best. The results produced six candidates which scientists then tested in stem cell models.
The final tests filtered the results down to two compounds that targeted all three pathways involved in the development of Alzheimer’s disease. The team now hopes to gain funding to further their research by optimizing these new compounds into drug candidates for pre-clinical and clinical studies.
The findings appear in the journal Chemical Science.
SWNS writer Laura Sharman contributed to this report.