Peptide nasal drops show potential to revolutionize treatment and recovery times for stroke victims

The peptide has been linked to neurodevelopment and quick recovery. 

Revolutionizing treatment

A multicenter study in which researchers at the Universities of Gothenburg and Cologne implemented parallel testing of an experimental stroke treatment on mice. The study was conducted in collaboration with researchers at the Czech Academy of Sciences.

The research uncovered contrasting effects on functional recovery after ischemic stroke when using the C3a component. It shows inhibition in the acute phase and facilitation in the later phase, the Journal of Clinical Investigation (JCI) reported. 

Scientists saw mice recover motor functions faster and better after stroke when given C3A nasal drops, compared to mice that received a placebo nasal treatment.

The treatment was initiated seven days post-stroke.

Marcela Pekna, Professor of Neuroimmunology at Sahlgrenska Academy says, “With this method, there’s no need to race against the clock. If the treatment is used in clinical practice, all stroke patients could receive it, even those who arrive at the hospital too late for thrombolysis or thrombectomy." 

Pekna, also the leader of the study, adds that the nasal drops could be given to those individuals with remaining disability after the clot is removed and could show signs of improvement too. 

Medicinal impact

A University of Gothenburg statement said that researchers were able to identify the underlying cellular and molecular processes in the brain through the treatment. 

“Magnetic resonance imaging (MRI) showed that the treatment with C3a peptide increased the formation of new connections among nerve cells in the mouse brains,” the press release states. 

However, some contradictory effects were observed where timing played an important role in C3a peptide treatment. The molecule can increase the amount of inflammatory cells in the brain if given too soon. 

Milos Pekny, Professor at the University of Gothenburg clarifies that the C3a peptide affects the function of astrocytes. He said, “cells that control many of the nerve cells' functions in both the healthy and the diseased brain — and which signals astrocytes send to nerve cells.”

The medication is currently being developed collaboratively by scientists from the Swedish University of Gothenburg, the German University of Cologne, and the Czech Academy of Sciences.

Professor Marcela Pekna voices that the important thing is the good effect remains. 

“Our ambition is to develop the method to make it usable in clinical practice, but to get there, and especially to be able to carry out the necessary clinical trials, we need to team up with a partner in the pharmaceutical industry,” she said.

Study Abstract

Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR–/–) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR–/–mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.