MJFF Grants Supports Early Work Into IC 100 in Treating Parkinson’s
ZyVersa Therapeutics announced that a grant from the Michael J. Fox Foundation for Parkinson’s Research (MJFF) will support work into IC 100 as a potential antibody-based therapy for Parkinson’s disease.
Robert Keane, PhD, and Juan Pablo de Rivero Vaccari, PhD, professors at the University of Miami Miller School of Medicine and its Miami Project to Cure Paralysis, want to understand if alpha-synuclein protein aggregates trigger the activation of inflammasomes, multiprotein complexes involved in inflammatory responses.
The grant, whose amount was not specified, supports preclinical studies to determine if blocking inflammasomes with IC 100 can prevent neuroinflammation in Parkinson’s. The two scientists are credited with inventing the experimental therapy.
“We are optimistic in funding ZyVersa’s research to further our understanding of neuroinflammation pathways and to see if the IC 100 inhibition of inflammasomes will block the gateway of activation,” Jessica Tome-Garcia, PhD, associate director of research programs at the MJFF, said in a company press release.
In Parkinson’s disease, the accumulation of toxic misfolded alpha-synuclein protein in dopamine-producing nerve cells causes them to die or malfunction. Dopamine is a chemical messenger, or neurotransmitter, that allows nerve cells to communicate.
Preventing neuroinflammation in Parkinson’s disease is goal
Studies suggest that neuroinflammation and microglia activation drive disease development. Microglia are considered the immune cells of the brain, protecting it from pathogens. But they can also lead to neuroinflammation when overactivated.
Inflammasomes are made up of three basic proteins: a sensor molecule like NLRP3 that responds to different stimuli, an adaptor ASC protein, and pro-caspase 1. Inflammasomes activate the inflammatory response by assembling into a large protein complex known as ASC Specks, triggering the release of a potent pro-inflammatory cytokine called IL-1 beta.
IC 100 is monoclonal antibody designed to bind and block ASC proteins, as well as ASC Specks, thereby inhibiting the initiation and continuation of inflammation, the company reported.
“In animal models of multiple sclerosis, aging, traumatic brain injury, spinal cord injury, and stroke, IC 100 has been shown to interfere with [central nervous system] inflammasome signaling, resulting in improved [physiological] and behavioral outcomes,” said Stephen Glover, co-founder, CEO, and chairman of ZyVersa.
“This research will help determine the potential of IC 100 (inflammasome ASC inhibitor) to block the damaging neuroinflammation that induces neural degeneration in Parkinson’s disease, similar to what we have seen in other [central nervous system] conditions,” he added.
Researchers aim to verify for a first time if alpha-synuclein preformed fibrils, a lab-made form of the alpha-synuclein protein, and ASC specks trigger the activation of microglial inflammasomes and if IC 100 can block this activation.
“We are grateful to The Michael J. Fox Foundation for funding this research,” Keane said.
Keane and Vaccari are members of a ZyVersa scientific advisory board.