MJFF Supports Work on RRx-001, Targeting Neuroinflammation

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by Patricia Inácio, PhD |

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A $500,000 grant from the Michael J. Fox Foundation for Parkinson’s Research (MJFF) to EpicentRx will support continuing work into the neuroprotective effects of RRx-001, its lead small molecule treatment for Parkinson’s disease.

RRx-001 works by blocking the activation of the NLRP3 inflammasome, known to play a key role in promoting the inflammatory responses that are increasingly recognized as drivers of Parkinson’s.

Chronic inflammation in the brain (neuroinflammation) is believed to contribute to the loss of dopamine-producing nerve cells, particularly in the substantia nigra, a brain region involved in the control of voluntary movement.

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The inflammasome is a multiprotein complex responsible for the activation of inflammatory responses that works as a sensor of environmental and cellular stress. Recent research has suggested that activation of one such inflammasome, called NLRP3, is a significant driver of Parkinson’s progression.

By blocking the NLRP3 inflammasome, RRx-001 could help to lower chronic inflammation and slow or halt Parkinson’s progression.

“MJFF continues to invest in research that will improve our understanding of inflammasome inhibitors used to reduce or reverse symptoms of Parkinson’s disease. We are pleased to award this grant to EpicentRx to increase our understanding of RRx-001,” Shalini Padmanabhan, MJFF’s vice president of research programs, said in a press release.

NLRP3 inflammasome as treatment target

With this grant, co-funded by the Shake it Up Australia Foundation, EpicentRx will partner with Richard Gordon, PhD, a neuroscientist researcher at The University of Queensland in Brisbane, Australia.

Gordon, considered an expert on the role of neuroinflammation and inflammasome activation in Parkinson’s disease, led previous research into the role of inflammasome activation in Parkinson’s and the potential of NLRP3 as a therapeutic target. This work was funded by a separate MJFF grant and a student fellowship awarded by the Parkinson’s Foundation.

“We are thrilled and honored to have received support from The Michael J. Fox Foundation’s flagship therapeutics program and to have the opportunity to work closely with an experienced Parkinson’s researcher like Dr. Gordon,” said Tony R. Reid, MD, PhD, EpicentRx’s CEO.

RRx-001, developed with EpicentRx’s CyNRGY platform of small molecules, binds to a particular amino acid, called cysteine, in immune and red blood cells. RRx-001 inhibits the NLRP3 inflammasome while also promoting the activation of the Nrf2 pathway, which has anti-inflammatory activities among its roles.

According to EpicentRx, its synergistic activity supports a “mechanism of neuroprotection in the brain, blood/vascular and immune system which are affected” by Parkinson’s disease.

“RRx-001’s inhibition of the inflammasome represents exciting new potential for the treatment and prevention of chronic inflammation-driven diseases such as Parkinson’s disease,” Reid said.

RRx-001 is being evaluated in a Phase 3 clinical trial (NCT03699956) as a potential add-on treatment to platinum chemotherapy in people with small cell lung cancer (SCLC).

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