RNA mimic blocks pain at a molecular level


Thursday, 18 January, 2018

RNA mimic blocks pain at a molecular level

Researchers at The University of Texas at Dallas are using RNA-based medicine to combat one of the most pervasive of human health conditions — pain.

Dr Zachary Campbell directs the Laboratory of RNA Control at the university, where he studies pain on a molecular level. He noted, “If you have ever hit yourself with a hammer, afterward, even a light touch can be painful for days or even weeks.

“To promote healing, our nervous system catalogues our sensory experiences and, under normal circumstances, eventually forgets. Defects in this process can result in chronic pain — a root cause of enormous suffering.”

Together with Dr Ted Price, Dr Michael Burton and colleagues, Dr Campbell has developed a new method of reducing pain-associated behaviours using RNA-based medicine. He and his team have taken the approach of blocking the creation of the proteins that set pain in motion, through the creation of a new class of decoy molecules.

“When you have an injury, certain molecules are made rapidly,” said Dr Campbell. “With this Achilles heel in mind, we set out to sabotage the normal series of events that produce pain at the site of an injury. In essence, we eliminate the potential for a pathological pain state to emerge.”

After an injury, instructions provided by the genome — the full set of genetic instructions present in each cell — are translated to create pain-signalling proteins. Those instructions are encoded in molecules called messenger RNA (mRNA).

The team’s decoy interrupts the pain-protein synthesis process that mRNA facilitates, reducing signs of inflammation and impairing pain behaviours. Their RNA mimic has since been injected at the site of an injury in experiments on mice, in a study published in the journal Nature Communications.

“Our results indicate that local treatment with the decoy can prevent pain and inflammation brought about by a tissue injury,” said Dr Campbell.

One huge hurdle in creating such an RNA-based compound was overcoming the rapid metabolism of the molecules, with Dr Campbell noting, “Molecules that degrade quickly in cells are not great drug candidates.

“The stability of our compounds is an order of magnitude greater than unmodified RNA,” he claimed.

Dr Campbell emphasised the importance of treating pain at the site of an injury, as a major problem with drugs that interact with the central nervous system is that they also can affect the reward centre of the brain.

“The ongoing opioid crisis highlights the need for pain treatments that don’t create addictions,” he said. “Hopefully, this is a step in that direction.”

Dr Campbell believes his team’s effort proposes a new method of treating a broad range of medical issues, claiming theirs is “the first attempt to create a chemically stabilised mimic to competitively inhibit RNA to disrupt RNA-protein interactions”.

“Our approach suggests that targeting those interactions may provide a new source of pharmacological agents,” he said. “This proof of concept allows us to open a whole new area of science by virtue of the route that we’re attacking it.”

Image credit: ©stock.adobe.com/au/yodiyim

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