FightMND Supports ALS Research on Inflammasome Blocker RRx-001

RRx-001's potential neuroprotective effects also being tested for Parkinson's

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

Share this article:

Share article via email
An illustration of money growing on vines.

EpicentRx has been awarded funding from FightMND to study how well RRx-001, its lead small molecule, may protect nerve cells against damage caused by amyotrophic lateral sclerosis (ALS), a disease also known as motor neuron disease (MND).

“We are very pleased to receive this support from FightMND and share their mission to finding effective treatments for neurodegenerative diseases such as MND,” said Tony R. Reid, MD, PhD, CEO of EpicentRx, in a company press release.

Recommended Reading
A coin drops into the top slot on a red piggy bank.

Via Orphan Drug Grant Program, FDA Funds New ALS Research

What is RRx-001?

RRx-001, which is in Phase 3 trials for the treatment of small cell lung cancer, binds to cysteines (a type of building block that makes up proteins) found on the surface of immune and red blood cells.

Once it crosses to the inside of these cells, RRx-001 works in part by blocking the NLRP3 inflammasome, a group of proteins that can sense danger and help mount an inflammatory response for protection.

It is thought that the NLRP3 inflammasome may set off too strong an inflammatory response in settings of disease, which may contribute to the progressive nerve cell damage that occurs in neurodegenerative diseases such as ALS.

At the same time, RRx-001 activates Nrf2, a protein that helps protect the cells against damage caused by oxidative stress. Oxidative stress occurs when the production of potentially harmful oxidant molecules surpasses the ability of cells to clear them with antioxidants.

The two actions combined may help protect nerve cells against damage and ease the symptoms of ALS and other neurodegenerative diseases.

“By targeting multiple mechanisms with the same drug, we will maximize our chances of being able to slow or halt MND progression in the clinic,” said Richard Gordon, PhD, who is leading the RRx-001 research program.

Gordon is an associate professor at Queensland University of Technology’s Translational Research Institute and Centre for Microbiome Research in Brisbane, Australia.

Joining Gordon in the research will be Pamela McCombe, MD, PhD, and Robert Henderson, MD, PhD, two neurologists from the Royal Brisbane and Women’s Hospital.

This funding is vital to broadening our understanding of how RRx-001’s inhibition of the inflammasome may change the course of treatment and prevention of chronic inflammation-driven diseases such as Parkinson’s and MND.

Earlier this year, EpicentRx received a $500,000 grant from the Michael J. Fox Foundation for Parkinson’s Research to study the neuroprotective effects of RRx-001 in Parkinson’s disease.

Early data from this study, co-funded by Shake it Up Australia, was presented at the annual Neuroscience 2022 conference, which was held Nov. 12–16 in San Diego.

In the presentation, titled “The NLRP3 inhibitor RRx-001 crosses the blood brain barrier and alleviates neuroinflammation in experimental models of Parkinson’s disease,” a team of researchers led by Gordon showed RRx-001 can cross the blood-brain barrier in rats and can block the NLRP3 inflammasome in microglia and macrophages, two types of immune cells.

“This highlights the neuroprotective properties of RRx-001 as a novel disease-modifying agent for [Parkinson’s] and other neurodegenerative diseases linked to NLRP3-driven [disease],” the researchers wrote.

Now, the funding from FightMND will go to continuing work on RRx-001 and its potential neuroprotective effects.

“This funding is vital to broadening our understanding of how RRx-001’s inhibition of the inflammasome may change the course of treatment and prevention of chronic inflammation-driven diseases such as Parkinson’s and MND,” Reid said.