Compound improved stroke recovery by reducing damaging inflammation

By John Murphy, MDLinx
Published May 1, 2018

Key Takeaways

An experimental compound appeared to improve stroke recovery in rats by reducing the continuing inflammation that contributes to secondary damage from stroke, researchers reported in a recent study published in Journal of Cerebral Blood Flow and Metabolism.

Researchers administered compound 21—a highly selective, non-peptide angiotensin type 2 receptor agonist—in male rats after an embolic stroke, but they found that the treatment had no effect on the acute features of stroke. However, rats given compound 21 did show memory and motor improvements in the days and weeks following stroke.

“We don’t see acute neuroprotection, but it definitely affects long-term outcome,” said senior author Adviye Ergul, MD, PhD, vascular physiologist and Regents’ Professor, Department of Physiology, Medical College of Georgia, Augusta University, Augusta, GA. “We think it will help the recovery and, at this moment, we really have no drugs to do that.”

More people are surviving stroke, thanks to better acute management and more effective prevention. However, stroke survivors are often left with sequelae such as cognitive deficits and impaired ability to function, Dr. Ergul said.

“Our evidence to date indicates that compound 21 helps directly address lingering inflammation and its destructive impact,” said senior author Susan Fagan, PharmD, assistant dean, University of Georgia College of Pharmacy, and Albert W. Jowdy Professor and director, Center for Pharmacy and Experimental Therapeutics, Medical College of Georgia.

Currently, compound 21 (developed by Vicore Pharma, Mölndal, Sweden) is in clinical trials for the treatment of idiopathic pulmonary fibrosis.

For this randomized, controlled, blinded preclinical trial, the researchers instigated embolic stroke in 257 male rats. Then, they intravenously administered different doses of compound 21 or saline for 5 days, with the first dose given 3, 6, or 24 hours after stroke. Some rats also received tissue plasminogen activator (tPA) at either 2 or 4 hours after stroke and compound 21 at 3 hours.

Neither compound 21 alone or in combination with tPA reduced the size of the stroke, researchers found. However, when compared with rats given only saline, the rats given compound 21 had less brain inflammation, performed better on memory tests, and had better nerve and movement function in the days following stroke. Even the lowest dose of the compound administered 3 hours after stroke resulted in significant improvement in these functions. In subsequent studies, the researchers found that the compound reduced inflammation when given as late as 24 hours after stroke.

The researchers speculate that the compound not only inhibits inflammation and oxidative stress, but also stimulates production of nitric oxide and brain-derived neurotrophic factor. In follow-up studies, they are administering the compound up to 7 days after stroke to investigate how well it can provide long-term cognitive benefits.

This research was supported by the National Institutes of Health and the Department of Veterans Affairs. Vicore Pharma supplied compound 21.

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