A new nasal spray may hold the key to saving people from both epilepsy and Alzheimer’s disease. Researchers from the Medical College of Georgia at Augusta University say the spray uses a novel peptide that boosts the brain’s ability to prevent seizures and protect neurons.
Specifically, the team developed the A1R-CT peptide which shows the ability to tamp down uncontrolled electrical activity in the brain. This is a common problem after a traumatic brain injury or stroke, as well as a symptom affecting more than half of all Alzheimer’s patients.
Neuropharmacologist Dr. Qin Wang adds that the development of a nasal spray could turn A1R-CT into a seizure rescue medication. The drug would be able to interrupt epileptic seizure clusters — where debilitating seizures in epilepsy patients occur back-to-back.
How does the peptide work?
A1R-CT inhibits neurabin, a protein that ensures the brain’s protective mechanism reduces hyperexcitability in the neurons, so the protein doesn’t overdo this. The peptide gets its name from the protective adenosine 1 receptor on the surface of neurons. Adenosine, a chemical mainly produced to neuron-supporting glial cells in response to hyperexcitability, activates this receptor.
“This is a powerful receptor to then silence the neurons,” Wang says in a university release.
Study authors add that this naturally calming relationship also blocks electrical activity that can cause an irregular heartbeat. Moreover, an injectable form of adenosine already exists and helps to treat people with very high heart rates.
“But the A1 receptor itself has to be regulated because if it’s activated too much, you will fall asleep. 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,” Wang adds, noting that caffeine blocks the A1 receptor.
While memory loss is a more common symptom, Alzheimer’s can also cause seizures when the buildup of amyloid and tau proteins disrupts communication between neurons in the brain. This also leads to more oxidative stress and inflammation, making neurons hyperexcited.
“In Alzheimer’s there are so many things that go wrong,” Wang says.
Unleashing A1’s power
Study authors note the A1 receptor’s activation by adenosine is something that’s pervasive throughout the human body, making the risk for side-effects highly likely. This is where neurabin comes into play. The study reveals that since neurabin is primarily in the brain, it provides the balance to prevent hyperactivity of the A1 receptor.
“Neurabin is a brake, so it doesn’t do too much,” Wang explains. “But now we need to remove it to unleash A1’s power.”
With that in mind, the team developed a peptide that can interfere with the A1 receptor and neurabin’s interaction — creating a more naturally protective effect that reduces seizures.
A1 receptor activation calms down the excited neurons by altering their ion channels — proteins in the cell that allow for the passage of other proteins around the cell. This process helps to generate healthy electrical signals in the cells. The result is called hyperpolarization, meaning neurons are less likely to fire an electrical signal.
“The more polarized the neurons are, the harder it is for them to get excited,” Wang says.
Activating the A1 receptor also reduces the release of glutamate, a neurotransmitter that neurons produce — which also excites those same neurons. The study found a dramatic reduction in the death of neurons among Alzheimer’s patients after using the peptide.
By inhibiting neurabin, the peptide enables A1C to reduce excessive electrical activity in the brain. In lab mice suffering from severe seizures, injecting them with the peptide lowered their symptoms.
Turning the peptide into an easy-to-use nasal spray
The scientists found similar results among seizure and Alzheimer’s models after turning the original injection into a nasal spray.
To emphasize the importance of neurabin, study authors say mice with a neurabin deficiency had significantly shorter and less severe seizures. Moreover, all of the mice survived.
However, those with normal neurabin levels experienced seizures that lasted for up to 30 minutes and 10 percent of the mice died after their episodes. Blocking the A1 receptor in neurabin-deficient mice led to more than 50 percent of the mice dying from their seizures.
The team is now exploring the ideal doses and delivery times to treat certain conditions with this peptide. They are continuing to tweak the nasal spray while they pursue funding to begin clinical trials.
The study is published in the journal JCI Insight.