Alzheimer’s, which is a neurological condition, gradually kills brain cells.
This plan is the result of joint work between the University of Cambridge in the United Kingdom and Lund University in Sweden.
A paper about the study is shortly to appear in Proceedings of the National Academy of Sciences.
Hundreds of clinical trials have assessed drugs for Alzheimer’s disease but none specifically targeted the pathogens responsible, the investigators say.
“Until very recently,” says senior study author Michele Vendruscolo, a professor in the Department of Chemistry at Cambridge, “scientists couldn’t agree on what the cause was so we didn’t have a target.”
“As the pathogens have now been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to aim drugs at these toxic particles,” he adds.
The new strategy shows not only that is there a way to design compounds that target the toxic protein clumps, but also how to make them more potent.
Toxic ‘rogue’ proteins
An estimated 5.7 million people in the United States have dementia caused by Alzheimer’s disease. This number is expected to more than double over next 30 years.
In the U.S., as in the U.K., Alzheimer’s is the only disease in the top 10 causes of death for which there are no treatments that prevent, slow, or cure it.
As the condition progresses, killing brain cells and tissue, the brain shrinks. This is accompanied by symptoms ranging from memory loss to personality change. Eventually, it robs people of their ability to do everyday tasks and live independently.
Proteins are molecules that make up the structure of organs and tissues and carry out many jobs in the body, including inside and between cells.
The molecules are large, complex 3-D chains formed of hundreds to thousands of amino acid units, of which there are 20 different chemical types.
In Alzheimer’s disease, toxic deposits of “rogue” proteins kill healthy brain cells. This happens, for example, when the protein fails to fold, or stay folded, in the correct 3-D shape.
‘Waste disposal’ mechanisms cannot keep up
“Misfolded and aggregated proteins” are linked not only with Alzheimer’s, but also with Parkinson’s and many other human diseases.
The brain has “waste disposal” mechanisms for clearing away such rogue proteins. However, Prof. Vendruscolo explains, “As we age, the brain becomes less able to get rid of the dangerous deposits, leading to disease.”
Another study recently identified genes that link the brain’s waste disposal system to Alzheimer’s disease.
The scientists at Cambridge have now founded a biotechnology company to apply their research to finding new diagnostics and treatments for Alzheimer’s disease and other disorders that arise from misfolded proteins.
They expect to begin clinical trials with the first batch of candidate drugs in approximately 2 years’ time.
The researchers developed the new strategy using an approach called chemical kinetics, which is particularly suitable for examining the “highly dynamic” process of toxic protein aggregation and pinpointing its source.
“This is the first time that a systematic method to go after the pathogens — the cause of Alzheimer’s disease — has been proposed.”
Prof. Michele Vendruscolo