Neurology Central

Neurological imaging: new FRW molecule able to bind to blood vessels

Researchers have developed FRW, a peptide that can bind to blood vessels without binding to other organs; this could lead to novel imaging techniques for neurodegenerative diseases.

Researchers from the University of São Paolo (São Paolo, Brazil), have developed a molecule known as FRW, that when injected into the bloodstream was able to bind to blood vessels in the brain and no other organs, producing the first complete map of the vasculature of the brain. This could possibly lead to novel methods of diagnostic imaging.

Currently, the development of novel drugs with the ability to bind to blood vessels in the brain is the blood–brain barrier (BBB), which acts as a boundary to stop toxic substances encountering the central nervous system. However, this study indicates that FRW can bind to the BBB.

In this study, published in Proceedings of the National Academy of Sciences, researchers utilized a technique known as phage display. A library of bacteriophages was altered, so that each one had a different surface peptide compared with the original virus. These peptides carry markers that can be detected when they bind to specific proteins. The researchers injected mice with approximately 10 billion of these bacteriophages.

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Although most of the bacteriophages were eliminated by the mice, some were able to bind to the BBB. These were collected from the brain and cultured in bacteria. The next-generation bacteriophages were then injected into mice. After three repeats of this, the researchers had roughly 3000 bacteriophages with the ability to bind to blood vessels in the brain.

Just over one-third of the peptides that bound to the BBB contained a sequence of three amino acids, phenylalanine, arginine and tryptophan (FRW). The researchers revealed that this sequence could bind to brain blood vessels, but importantly, didn’t bind to blood vessels in other tissues. Surprisingly, FRW also didn’t bind to blood vessels in the retina.

Ricardo José Giordano (University of São Paolo), who led the research, explained: “the barrier that protects blood vessels in the retina was believed to be very similar or even identical to the blood-brain barrier, but we discovered a difference, at least in mice, thanks to this molecule.”

The researchers were able to see the bacteriophages bound to the brain blood vessels using electron microscopy. Combining these techniques is an effective way of identifying a phage target in vivo.

These exciting results are likely to pave the way for future research. The researchers anticipate that this novel technique could be utilized to spot gaps in the BBB that could potentially lead to neurodegenerative diseases, such as Alzheimer’s disease.

“Theoretically speaking, if FRW doesn’t bind to the cerebrovascular system, it’s a sign that the barrier is impaired,” Giordano concluded.

The next step is to determine whether a synthetic version of the peptide will work in the same way. So far, this hasn’t been observable in vivo. Further research on other peptides that bind to specific brain regions could also be useful and may lead to more precise diagnostic tests in the brain.

Sources: Tang FHF, Staquicini FI, Teixeira AAR et al. A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina. PNAS 116(6), 2300–2305 (2019);