[ad_1]
A world first for Alzheimer's disease by Cambridge scientists could target the cause of the disease and lead to a new generation of drugs that could be the subject of clinical trials in two years.
With Swedish scientists, they discovered a new way to target toxic particles that destroy healthy brain cells.
Professor Michele Vendruscolo, from the University, said: "All previous clinical trials that focused on finding drugs to change the disease have failed.
"Successful trials have given us a handful of medications, but these drugs can only treat the symptoms of Alzheimer's disease, not its onset and progression.
"As pathogens have been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to target drugs on these toxic particles.
"Our research is based on the main conceptual step of identifying protein oligomers as pathogens and presents a method for systematically developing compounds to target them.
"This approach allows for a new drug discovery strategy.
"This is the first time that a systematic method of controlling pathogens, the cause of Alzheimer's disease, is proposed.
"Until very recently, scientists could not agree on the cause, so we had no target.
"We have devised the first strategy to" tackle the cause of the disease, hoping that new drugs can be developed. "
(Image: Andrii Vodolazhskyi)
Dementia is the leading cause of death in the UK and the cost of dementia is expected to more than double in the next 25 years, from 26 to 55 billion pounds.
Scientists have identified abnormal deposits called protein oligomers as the most likely cause of dementia.
Although proteins are normally responsible for important cellular processes, in the case of Alzheimer's disease, these proteins become indelicate, form clumps and destroy healthy nerve cells.
Alzheimer's disease causes nerve cell death and tissue loss in the brain.
Over time, the brain contracts dramatically and the destruction of cells causes memory failure, personality changes, and problems with daily activities.
Proteins must bend properly to be effective and when they fold poorly, dangerous deposits, called plaques, that the brain can not move and cause dementia.
Plates accumulate between nerve cells, preventing them from reporting properly. As the nerve cells die, they twist, causing even more damage when they block nutrients and other cell stores.
Professor Vendruscolo explained, "A healthy brain has a quality control system that effectively removes potentially dangerous masses of protein called aggregates.
"As you get older, the brain becomes less able to get rid of dangerous deposits, leading to the disease.
"It's like a home recycling system, if you have an effective system in place, the clutter is eliminated quickly. If this is not the case, you accumulate slowly but regularly unnecessary waste. even in the brain. "
Video unavailable
The research was conducted by a team of scientists, including the University of Lund in Sweden, and also included Professor Sir Christopher Dobson, Master of St John's College of the University of Cambridge, at Center for Misfolding Diseases (CMD).
Their research article was published today in the Proceedings of the National Academy of Sciences (PNAS).
Sir Christopher said: "This interdisciplinary study shows that it is possible not only to find compounds that target toxic oligomers that cause neurodegenerative disorders, but also to increase their potency in a rational manner.
"It is now possible to design molecules that have specific effects on different stages of disorders such as Alzheimer's disease and, hopefully, convert them into drugs that can be used in a clinical setting."
Dementia costs the health and social services sector more than cancer and heart disease combined and receives a disproportionate amount of research investment.
In 2012, dementia research in the United Kingdom received six times less funding than cancer research.
(Image: E + / Getty Images)
There have been about 400 clinical trials on Alzheimer's disease, but none of them specifically targeted the causative pathogens.
In the United Kingdom, dementia is the only condition in the top 10 causes of death without treatment to prevent, cure or slow its progression.
The team estimates that their first drug candidates could be tested in clinical trials in about two years.
The new strategy is based on an innovative approach to chemical kinetics developed over the last ten years by scientists led jointly by Professor Tuomas Knowles, also a member of St John's College, Sir Christopher and Professor Vendruscolo, in collaboration with the new center with scientists from Lund University led by Professor Sara Linse.
Professor Knowles said, "We are very excited about the potential of chemical kinetics for drug discovery against protein folding diseases.
"Since the aggregation process is very dynamic, the framework of kinetics allows us to approach this problem in a new way and to find approaches to stop the generation of toxic protein species." at their very source. "
Dr. David Reynolds, Scientific Director of Alzheimer's Research UK, said: "This is a detailed academic study on how quickly the compounds are able to" find out. prevent amyloid from developing into toxic clumps, characteristic of Alzheimer's disease.
"In the absence of treatments to slow down or stop the diseases that cause dementia, it is essential to improve what kind of approaches that could help improve the progress of drug discovery and speed up new treatments for sufferers. "
Source link
