A Common Asthma Drug Shows Promise as a Treatment for Alzheimer’s

Alzheimer’s Disease takes hundreds of thousands of lives every year, affecting 47 million people worldwide. But so far, no amount of urgency, nor billions of dollars over decades into drug research, have yielded a treatment. Now, a new early-stage study has found that repurposing salbutamol for Alzheimer’s may hold “significant potential as a low cost and rapid response option,” according to a statement out of Lancaster University in England.

Synapses connect nerve cells in our brains, which are vital to the formation of memories. In Alzheimer’s, these connections fail, and the brain cells die. One of the primary biomarkers of Alzheimer’s is accumulations of insoluble protein fibers called tau, which, in the brains of people with the disease, accumulate in neurofibrillary tangles and kill the brain cells we rely on for memory. Symptoms progress as tau tangles accumulate. One theory for curing Alzheimer’s is that we must figure out how to stop tau protein tangles from forming and building up.

Via a special analytical technique called ‘Synchrotron Radiation Circular Dichroism’ (SRCD), researchers at Lancaster University were able to look at existing compounds of over 80 existing compounds and drugs to determine their effectiveness in combating tau.

What they found was that salbutamol — contains the compound epinephrine — effectively stabilized the proteins and prevented them from forming into tangles. When adding salbutamol to solutions containing tau, researchers observed the density of the tangles being drastically reduced.

“Our work highlights the potential impact of repurposing drugs for secondary medical uses, by discovering a novel therapeutic strategy that impedes the molecular pathology of Alzheimer’s disease, and which may have otherwise gone unstudied,” said Dr. David Townsend of Lancaster university, lead author of the study. “Salbutamol has already undergone extensive human safety reviews, and if follow up research reveals an ability to impede Alzheimer’s disease progression in cellular and animal models, this drug could offer a step forward, whilst drastically reducing the cost and time associated with typical drug development.”

The problem salbutamol’s key ingredient epinephrine, also known as adrenaline, is that the human body rapidly metabolizes epinephrine instead of absorbing it, so the next step in the research was to evaluate other available compounds with similar chemical structures. This yielded other drugs as possible candidates for Alzheimer’s treatment including etamivan, a respiratory stimulant; fenoterol, for acute asthma and other lung problems; dobutamine, which treats cardiogenic shock and severe heart failure.

Among these, Dobutamine showed some promise, but with short-lived effects, and one of its disadvantages is that it needs to be administered intravenously. Salbutamol, on the other hand, is easily ingested, absorbed into the brain, and remains in the body for several hours, which makes it a much more appealing prospect in the search for a cure.

It is yet to be determined just why salbutamol has a helpful impact on tau tangles. The researchers at Lancaster 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.

The study follows research out of Temple University in 2018 that found an asthma drug called zileuton had a desirable mitigating effect on tau in a mouse study, but in this case, it was because zileuton is a leukotriene inhibitor (a medicine that decrease inflammation by preventing the action of inflammatory molecules called leukotrienes). The effects of ephinephrine on inflammation are yet unknown.

A co-author on the Lancaster study, Professor David Middleton, added: “This work is in the very early stages and we are some way from knowing whether or not salbutamol will be effective at treating Alzheimer’s disease in human patients. However, our results justify further testing of salbutamol, and similar drugs, in animal models of the disease and eventually, if successful, in clinical trials.”

The team believes research on salbutamol and other asthma drugs, as well as different methods of administering these drugs, is warranted.