Alzheimer’s disease is the most common form of dementia, affecting 47 million people worldwide and its prevalence is expected to triple to more than 130 million cases by 2050.
No effective treatments that cure the disease or slow down its progression have been discovered.
In a recent study at Lancaster University, researchers found that the common asthma drug salbutamol may offer potential as a treatment for Alzheimer’s disease.
They found that repurposing an existing drug, salbutamol, offers significant potential as a low cost and rapid response option.
They found that salbutamol is effective at reducing the accumulation of insoluble fibers of the tau protein—which is found in the brains of people with Alzheimer’s disease.
These microscopic fibers accumulate into neurofibrillary tangles and can cause neuron destabilization, brain cell death, and are a key characteristic of the disease’s progression.
The study is published in ACS Chemical Neuroscience. One author is Dr. David Townsend from Lancaster University.
Much Alzheimer’s disease research has focused on the build-up of amyloid plaques, caused by misfolding of the amyloid-β protein.
However, because of disappointing results from numerous therapies targeting Aβ aggregation, more attention is shifting towards tau.
In the study, the researchers used a new automated ‘high throughput’ screening approach to study the structure of the misfolding tau protein.
With this powerful technique, they were able to look at a selection of more than 80 existing compounds and drugs simultaneously to determine their effectiveness at preventing the formation of tau fibrils.
This method confirmed the compound epinephrine, more commonly known as adrenaline, was effective at stabilizing the tau proteins and preventing the formation of tau tangles.
However, our bodies do not easily absorb epinephrine and it rapidly gets metabolized, so the scientists then looked at a range of readily available compounds with similar chemical structures.
This search revealed four current drugs as possible candidates—etamivan, fenoterol, dobutamine, and salbutamol.
The team then found etaminvan and fenoterol have little effect on the assembly of tau tangles. Dobutamine, which is used for the rapid treatment of heart attacks and heart failure, was found to have some benefit.
However, because its effects are very short-lived, and because it needs to be administered intravenously, it is not ideal as a basis for the treatment of Alzheimer’s disease.
Further tests using a range of analytical techniques all revealed salbutamol could inhibit tau aggregation in vitro.
Tests where salbutamol was added to solutions containing tau resulted in a drastically reduced density of fibrous tau structures responsible for the tau neurofibrillary tangles.
The researchers believe that salbutamol interacts with an early stage of tau fibril formation, reducing their ability to form an initial nucleus which drives the aggregation process.
Because it is easily ingested, absorbed into the brain, and remains in the body for several hours, salbutamol has attractive properties as a research avenue for a potential new treatment for Alzheimer’s.
The researchers say that current asthma inhalers result in only a small amount of salbutamol reaching the brain and so if further research is successful, a new delivery method would also need to be developed.
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