Absence of immune stimuli
Immune stimuli
NLRP3 inhibitors
A key mediator of chronic inflammation that develops with age
NLRP3 is a critical component of the inflammasome, a protein complex that assembles in response to infection and tissue damage and results in inflammation needed to promote healing. However, chronic inflammasome activation leads to pathologic inflammation that drives a vast number of immunologic and fibrotic disorders. Analysis of BioAge’s proprietary longitudinal human aging cohorts revealed that NLRP3 levels rise with age are associated with all-cause mortality.
BioAge has discovered a family of chemically novel NLRP3 inhibitors. We are developing two compounds in parallel–one that enters the central nervous system, and the other that is topically delivered to the eye–to optimize our ability to address the many age-related diseases driven by chronic inflammasome activation.
Discoverу
Lead Op
IND-enabling
CNS oral product
Neuroinflammation
Planned lead: Parkinson's
Planned lead: Parkinson's
Ocular topical product
Ocular inflammation
Planned lead: Dry eye disease
Planned lead: Dry eye disease
BioAge’s novel NLRP3 inhibitors correct chronic
inflammasome activation that is associated with
aging and drives a broad range of diseases
BioAge’s novel NLRP3 inhibitors correct
chronic inflammasome activation that is
associated with aging and drives a
broad range of diseases
BioAge’s novel NLRP3 inhibitors
correct chronic inflammasome
activation that is associated with
aging and drives a broad range of
diseases
BioAge’s novel NLRP3 inhibitors correct chronic
inflammasome activation that is associated with
aging and drives a broad range of diseases
BioAge’s novel NLRP3 inhibitors correct
chronic inflammasome activation that is
associated with aging and drives a
broad range of diseases
BioAge’s novel NLRP3 inhibitors
correct chronic inflammasome
activation that is associated with
aging and drives a broad range of
diseases
Young
Inactive NLRP3
NLRP3 inflammasome assembly and activation
Acute cytokine release:
(IL-1β, IL-18)
Acute inflammation to enable immune respons to pathogen
Old
Overactive NLRP3 inflammasome
Immune system priming:
↑ NLRP3, ASC, pro-caspase
-
NLRP3
-
ACS
-
Pro-caspase-1
Exaggerated proinflammatory signals:
Cytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3 inhibitor
Prolonged inflammation, even in the absence of pathogen
Acute cytokine release:
(IL-1β, IL-18)
Acute inflammation to enable immune respons to pathogen
Exaggerated proinflammatory signals:
Cytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3 inhibitor
Prolonged inflammation, even in the absence of pathogen
BioAge collaborator spotlight
Chronic activation of the NLRP3 inflammasome is associated with aging and is a major contributor to the pathologic inflammation that drives or exacerbates multiple metabolic, immunologic, and fibrotic disorders, as well as neurodegenerative conditions such as Parkinson’s and Alzheimer’s. Inhibition of NLRP3 using small-molecules thus has the potential to treat a broad spectrum of age-related diseases.
Rebecca Coll, PhD
Wellcome Wolfson Institute for Experimental Medicine
Queen's University Belfast
