- A team of scientists have discovered two new compounds which are early leads for drugs to treat Alzheimer鈥檚 Disease
- Unlike other treatments for this complex disease, the new compounds target multiple biological pathways involved in the development of Alzheimer鈥檚 Disease
- Alzheimer鈥檚 Disease is the most common form of dementia and is responsible for 80 per cent of all dementia cases
- The new approach could be used for other diseases with complex causes like cancer
Scientists at the University of 葫芦影业 have developed a new approach to creating drugs to treat Alzheimer鈥檚 disease which has identified two potential new therapies.
As we live longer, all forms of dementia are increasing. Alzheimer鈥檚 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 new drug leads, discovered by a multidisciplinary team and led by scientists at the University of 葫芦影业, are able to target the three pillars that cause Alzheimer鈥檚 disease, and improve on previous approaches to developing new treatments for the debilitating disease.
The causes of Alzheimer鈥檚 Disease are complex, but it is known that two rogue versions of natural proteins are involved. The first, called beta amyloid (A尾), 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 PrP岫, is responsible as when it binds to the rogue A尾 it leads to the distinctive cognitive impairment and neurotoxicity seen in Alzheimer鈥檚 disease.
Together, A尾, Tau and PrP岫 are seen as the three pillars which cause Alzheimer鈥檚 disease. Yet, most recent drug trials for Alzeimer鈥檚 Disease have only targeted A尾, by trying to prevent it causing plaques and inducing Tau to start tangling. This approach has so far proved to be unsuccessful.
The 葫芦影业 team has identified two new drug leads that not only bind to A尾, but block its interaction with PrP岫 and disrupts the formation of Tau tangles.
Professor Beining Chen, Professor of Medicinal Chemistry at the University of 葫芦影业, said: 鈥淥ver 50 million people are thought to be living with Alzheimer鈥檚 disease, despite recent clinical trials there have been no successful drug leads which target all three key players that cause this complex disease.
鈥淥ur 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鈥檚. Not only have we developed a new approach to creating treatments for Alzheimer鈥檚, we have identified two new drug leads.
鈥淲e are very pleased that this collective effort which has involved multiple academic and industrial partners has been so successful.鈥
The team was able to find these compounds through a multi-step molecular-sifting process. They began by using 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 A尾 best, leading to six lead candidates that were then tested in stem-cell models.
These final tests filtered the results down to two compounds that targeted all three pathways involved in the development of Alzheimer鈥檚 disease. The team now hopes to gain funding to further their research by optimising these new compounds into drug candidates for pre-clinical and clinical studies.
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葫芦影业's School of Mathematical and Physical Sciences
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