Scientists have developed a new peptide nasal spray that can help prevent seizures and reduce the risk of Alzheimer’s and epilepsy. The A1R-CT peptide nasal spray has the potential to be used as a seizure rescue medicine.
“A1R-CT works by inhibiting neurabin, a protein that helps ensure that the protective mechanism itself, which tamps down the hyperexcitability of neurons that disrupts normal communication and produces seizures, doesn’t overdo,” Explained Qin Wang, neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at the Medical College of Georgia at Augusta University. Wang was part of team that developed the A1R-CT peptide nasal spray.
A1R-CT is named after the protective adenosine 1 receptor on the surface of neurons. These receptors are stimulated by adenosine, a chemical made in the brain by neuron-supporting glial cells when hyperexcitability occurs. This receptor has a calming effect on the brain, blocking electrical activity that can cause an irregular heartbeat. Adenosine is also used to treat cases of high heart rate.
How will the peptide nasal spray work?
“But the A1 receptor itself has to be regulated because if it’s activated too much, you will fall asleep,” said Wang. “The neurons try to make sure everything stays in control and in most of us, it works pretty well. We don’t fall asleep at our desk. We don’t have seizures,” she added.
Seizures often occur in people who have Alzheimer’s due to a build-up in amyloid and tau proteins. These proteins disrupt communication between neurons, creating increased oxidative stress and inflammation. When this happens, neurons in the brain can become hyperexcited and become susceptible to seizures.
As the A1 receptor is activated by adenosine during hyperactivity, it is a logical treatment for seizures. However, its pervasive throughout the body could be an issue. Adenosine is found in the lungs, heart, and kidneys, meaning potential side effects are likely.
Wang and her colleagues discovered that the protein neurabin provides balance to the hyperactivity of the A1 receptor. As neurabin is primarily found in the brain, it is unlikely to cause any wider effects throughout the body. “Neurabin is a brake, so it doesn’t do too much, but now we need to remove it to unleash A1’s power,” said Wang. Wang and her team then began work on developing a peptide that could instead interfere with the interaction between the A1 receptor and the neurabin protein. If this could be achieved, the peptide nasal spray would provide a natural, seizure-reducing remedy.
When the A1 receptors are activated, they reduce the proteins in the cell membrane, allowing a passage through the cell for other proteins. This results in something called hyperpolarisation, meaning neurons are less likely to fire off the electrical signals which cause hyperactivity. “The more polarized the neurons are, the harder it is for them to get excited,” said Wang.
The clinical potential of the nasal spray
The scientists noticed a significant reduction in the death of neurons in their Alzheimer’s model with the use of their new peptide nasal spray. This proved that inhibiting neurabin with their peptide nasal spray enabled increased activity by the A1C, reducing the excessing electrical activity in the brain that causes seizures.
It was also discovered the peptide nasal spray was effective when injected into the brain or administered as a nasal spray. The accessibility of a nasal spray means the clinical potential of the peptide was able to be explored by scientists. Wang and her team will now continue research into the ideal dosage of the peptide nasal spray and delivery time for the specific conditions it will be used to treat. The team is currently pursuing the funding needed for further clinical trials ahead of the release of the peptide.
