Researchers recently developed a peptide called A1R-CT that could ultimately have therapeutic applications in both epilepsy and Alzheimer’s disease.
A new peptide administered through a nasal spray shows promising results as an anticonvulsant and could ultimately be further developed as a treatment to prevent seizures in both epilepsy and Alzheimer’s disease (AD).
A study published in The American Society for Clinical Investigation outlines work conducted by researchers to develop a peptide called A1R-CT that disrupts the signaling between the molecule neurabin and the adenosine 1 receptor (A1R). A1R sits on the outside of the neuron and responds to adenosine, whereas neurabin binds to the receptor and blocks it from use.
It has previously been established that A1R has neuroprotective effects and that, when activated by adenosine, it mediates an anti-convulsant response. This, however, is often blocked by neurabin.
“Neurabin is a brake, so it doesn’t do too much,” Dr. Qin Wang, neuropharmacologist and founding director of the program for Alzheimer’s therapeutics discovery at the Medical College of Georgia at Augusta University, told Science News. “But now we need to remove it to unleash A1’s power.”
It is a balancing act, though. While activating the receptor allows for A1R to be used as an anti-convulsant, “the A1 receptor itself has to be regulated because if it’s activated too much, you will fall asleep,” Wang explained.
To further investigate the effect of A1R and neurabin, the researchers experimentally blocked the A1R receptor in neurabin-deficient mice. These mice experienced more severe seizures, and the death rate increased by more than 50%.
They found that the mice that had a natural neurabin deficiency had significantly shorter and less severe seizures, and they all survived, whereas the mice with normal neurabin levels had worse seizures, and about 10% of them died shortly after.
After establishing this activity in mice, the researchers concluded that the A1R-CT peptide disrupts the neurabin-A1R interaction and allows A1R to work as an anti-convulsant and elicit an anti-seizure response.
Epileptic seizures are common after brain injury, stroke and with chronic neurological diseases such as AD. In fact, up to 64% of individuals who suffer from AD experience seizures.
These seizures vary in length and severity, but two types are more common than others: tonic-clonic seizures, during which the patient falls down, shakes and becomes unresponsive and focal onset, during which the patient experiences repetitive arm or leg movements, lip smacking and chewing.
There is an urgent need for novel therapies as seizures are uncontrolled by current medications and techniques in about 40% of people who experience them. When these seizures are left uncontrolled and untreated they often lead to brain damage and cognitive impairment.
When testing the A1R-CT peptide, the researchers found a dramatic decrease in neuron death in the Alzheimer’s model as well as an improvement in the severity, duration and death rate.
The peptide was effective both as an injection and as a nasal spray. The team’s next steps will be to work out dosing and tweaking the peptide so it can function optimally and, perhaps one day, be used as a rescue treatment for human patients suffering chronic seizures.
