PNAS is a way to make asthma medications last longer

For many people, inhalers are a miracle drug
.
From one minute of wheezing to the next minute of normal breathing, patients can experience significant relief
after one or two wheezing.
Few people realize that these life-saving drugs may actually fail in the long term, especially for people who
use them regularly and use them in large doses.

Researchers around the world have been looking for ways to improve inhaler delivery of drugs to be more effective and lasting, but so far with little
success.
A new study from the lab of lung scientist Dr.
Deepak Deshpande has found a new compound that can be added to existing drugs to bridge the gap
.

"Academia and industry have been actively pursuing this particular type of drug discovery approach for many years; To date, nothing has been found that shows the properties exhibited by Dr.
Deshpande's compound," said
Raymond Penn, Ph.
D.
, director of the Jefferson Center for Translational Medicine and co-author of the study.

Researchers have discovered a molecule that increases the potency of one of the main components of asthma inhalers, β agonists, whose purpose is to relax airway smooth muscle and open the contracted airways
.
Dr Penn, lead author of the study, explains: "When we make one drug more effective, we need fewer drugs to control symptoms
.
Fewer drugs also mean that a person is less likely to accumulate side effects that would stop the medication from working
.
We are very excited
about these results and how they can improve asthma medications.
The study was published in
PNAS.

Some anti-asthma drugs work by reducing inflammation of the lining of the airways, others work by reducing airway muscle contractions, and still others include a mixture
of both drugs.
Dr.
Deshpande's team is focused on β agonists because such drugs may eventually fail
.

Researchers are well aware of why these drugs fail.

Normally, β agonists land on receptors on the surface of muscle cells, like a baseball caught in a glove
.
This capture triggers a series of biochemical reactions within the cell, ultimately relaxing muscle tension
in the airways.
But once the drug is captured by the receptor, the receptor itself stops working and even degrades
over time.
It's as if the catcher has to leave the pitch every time he catches the ball, and the team has to use one less catcher
.

This is not a problem
if this medication is used occasionally.
But for people who regularly use this inhaler, the cells don't have enough time to produce new receptors
between inhalations.

Dr.
Deshpande's team at the Center for Translational Medicine is looking for a way to alter the way
receptors capture β agonists.
They developed a second compound that works
only after the β agonist lands on the receptor.
The second compound stabilizes the acceptor conformation
.
This essentially thickens the catcher's gloves and keeps her in the game
.

The researchers were able to show that when their compounds were delivered in mice along with β agonists, the strength of the drugs increased by 60-70 percent without a similar increase
in receptor degradation.
"In theory, this means that our compound could improve the therapeutic effect of β agonists, but we have more tests to do to see to what extent this approach improves the lifespan
of β agonists.
" But our findings are very impressive, and it is," Dr.
Deshpande said
.

Developing an add-on compound, rather than an entirely new anti-shrinkage drug, takes advantage of the fact
that β agonists have been used for years and are safe and effective for most people.
If future tests and clinical trials confirm the conclusions of this study, this new add-on drug may be delivered to patients
sooner than traditional new drugs.

Article reference: